Academic literature on the topic 'Pramipexolo'
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Journal articles on the topic "Pramipexolo"
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Mihaylova, Anita S., Ilia D. Kostadinov, Nina D. Doncheva, Hristina I. Zlatanova, and Delian P. Delev. "Effects of Pramipexole on Learning and Memory Processes in Naïve and Haloperidol-challenged Rats in Active Avoidance Test." Folia Medica 61, no. 2 (June 1, 2019): 258–65. http://dx.doi.org/10.2478/folmed-2018-0063.
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Abstract Background: Parkinson’s disease (PD) is the second most common neurode-generative disease, usually detected by its motor symptoms. The non-motor symptoms, including cognitive deficits, have been of great interest to researchers in the last few decades. Aim: To assess the effect of pramipexole on learning and memory in naïve and haloperidol-challenged rats. Materials and methods: Male Wistar rats divided into 9 groups (n=8): naïve - saline, pramipexole 0.5; 1 and 3 mg/kg bw; Haloperidol groups - saline, haloperidol, haloperidol + pramipexole 0.5; 1 and 3 mg/kg bw. Two-way active avoidance test (TWAA) and activity cage were performed. The studied parameters were: number of conditioned and unconditioned responses, vertical and horizontal movements. Statistical analysis was done using SPSS 19. Results: The naïve experimental groups significantly increased the number of conditioned responses during the tests for short- and long-term memory, compared with the saline groups (p<0.05). During the short-memory test only the animals with the lowest dose of PMX significantly increased the number of unconditioned responses whereas during the long-term memory test all experimental groups increased the number of escapes in comparison with the saline groups (p<0.05). Challenge dose of haloperidol attenuates learning and memory in pramipexol treated rats. Only the highest dose of pramipexol showed significant increase in conditioned and unconditioned responses compared with the haloperidol group (p<0.05). Conclusion: Pramipexole improves learning and memory in naïve rats by enhancing dopaminergic neurotransmission. This is probably not the only mechanism involved. This is confirmed by the decrease in learning and memory ability in rats with haloperidol-challenge.
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Chomaničová, Kamila, Štefan Husár, Miroslava Sýkorová, Katarína Birošíková, and Beáta Vladovičová. "Development of Pramipexole Prolonged-Release Matrix Tablets." Chemické listy 117, no. 1 (January 15, 2023): 17–22. http://dx.doi.org/10.54779/chl20230017.
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The present work deals with the development of a prolonged release matrix tablet of the readily soluble drug pramipexole. The new excipient Kollidon SR (a mixture of 80% polyvinyl acetate and 20% polyvinylpyrrolidone) and hypromellose K15M were used as polymers to control drug release from selected prototypes. Various polymer concentrations were tested to achieve a stable and pH independent release of pramipexole of 0.26 mg over 24 hours; samples were prepared by wet granulation and compression of matrix tablets. Drug release was monitored in dissolution media with pH values from 1.2 to 6.8 and compared with a reference product based on a hydrophilic matrix with a combination of three different polymers. The required release profile of the low-dose drug formulation was achieved using 60.0% (w/w) of Kollidon SR in all dissolution media and the selected formulation F2 demonstrated a sufficient alcohol resistance up to the ethanol concentration of 40% (v/v). Predložená práca sa zaoberá vývojom matricovej tablety s predĺženým uvoľňovaním ľahko rozpustného liečiva pramipexolu. Ako polymér riadiaci uvoľňovanie liečiva z vybraných prototypov bol použitý nový excipient Kollidon SR (zmes 80 % polyvinylacetátu a 20 % polyvinylpyrolidónu) a hypromelóza K15M. Testovali sa rôzne koncentrácie polymérov s cieľom dosiahnúť stabilné a pH nezávislé uvoľňovanie pramipexolu 0,26 mg po dobu 24 hodín, vzorky boli pripravené vlhkou granuláciou a lisovaním matricových tabliet. Uvoľňovanie liečiva bolo sledované v disolučných médiách s hodnotami pH od 1,2 až po 6,8 a porovnávané s referenčným prípravkom na báze hydrofilnej matrice s kombináciu troch rôznych polymérov. Požadovaný liberačný profil nízkodávkového liečiva bol dosiahnutý použitím 60,0 hm.% Kollidonu SR vo všetkých médiách a vybraná formulácia F2 vykazovala dostatočnú odolnosť aj voči pôsobeniu etanolu až do koncentrácie 40 obj.%.
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Sun, Yongqi, Baohong Cui, Lin Ye, Yunxin Hu, and Yujun Pan. "Pramipexole Inhibits Neuronal Apoptosis in Rats with Parkinson’s Disease." Journal of Healthcare Engineering 2022 (April 13, 2022): 1–5. http://dx.doi.org/10.1155/2022/7002630.
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To explore the inhibition of pramipexole on the neuronal apoptosis and its influences on the expressions of brain tissue brain-derived neurotrophic factor (BDNF), and serum miR-103a and miR-30b and inflammatory factors in rats with Parkinson’s disease. A total of 36 Sprague-Dawley rats were randomly divided into normal group (n = 12), model group (n = 12) and pramipexole group (n = 12). Compared with that in normal group, the positive expression of BDNF was substantially increased in model group and pramipexole group, and its positive expression in pramipexole group was notably higher than that in model group. The WB results revealed that compared with those in normal group, the relative protein expression levels of Bax and Bcl-2 were markedly increased and decreased, respectively, in the other two groups, and that pramipexole group exhibited a remarkable decline in the relative protein expression level of Bax and a considerable increase in that of Bcl-2, compared with model group. The relative expression levels of miR-103a and miR-30b in model and pramipexole groups were markedly higher than those in normal group, and pramipexole group had remarkably higher relative expression levels of miR-103a and miR-30b than model group. It was found through ELISA that model and pramipexole groups had markedly raised IL-1β and IL-18 content compared with normal group, and their content in pramipexole group was remarkably lower than that in model group. Based on the TUNEL results, compared with that in normal group, the apoptosis rate of cells rose substantially in the other two groups, and the apoptosis rate in pramipexole group was notably lower than that in model group. Pramipexole may up-regulate the expressions of BDNF, miR-103a and miR-30b to inhibit the apoptosis and inflammation in Parkinson’s disease model rats.
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Martens, Marieke Annie Gerdine, Alexander Kaltenboeck, Don Chamith Halahakoon, Michael Browning, Philip J. Cowen, and Catherine J. Harmer. "An Experimental Medicine Investigation of the Effects of Subacute Pramipexole Treatment on Emotional Information Processing in Healthy Volunteers." Pharmaceuticals 14, no. 8 (August 14, 2021): 800. http://dx.doi.org/10.3390/ph14080800.
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Treatment with the dopamine D2/D3 receptor agonist pramipexole has demonstrated promising clinical effects in patients with depression. However, the mechanisms through which pramipexole might alleviate depressive symptoms are currently not well understood. Conventional antidepressant drugs are thought to work by biasing the processing of emotional information in favour of positive relative to negative appraisal. In this study, we used an established experimental medicine assay to explore whether pramipexole treatment might have a similar effect. Employing a double-blind, parallel-group design, 40 healthy volunteers (aged 18 to 43 years, 50% female) were randomly allocated to 12 to 15 days of treatment with either pramipexole (at a peak daily dose of 1.0 mg pramipexole salt) or placebo. After treatment was established, emotional information processing was assessed on the neural level by measuring amygdala activity in response to positive and negative facial emotional expressions, using functional magnetic resonance imaging (MRI). In addition, behavioural measures of emotional information processing were collected at baseline and on drug, using an established computerized task battery, tapping into different cognitive domains. As predicted, pramipexole-treated participants, compared to those receiving placebo, showed decreased neural activity in response to negative (fearful) vs. positive (happy) facial expressions in bilateral amygdala. Contrary to our predictions, however, pramipexole treatment had no significant antidepressant-like effect on behavioural measures of emotional processing. This study provides the first experimental evidence that subacute pramipexole treatment in healthy volunteers modifies neural responses to emotional information in a manner that resembles the effects of conventional antidepressant drugs.
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Eisenreich, Wolfram, Bernd Sommer, Sebastian Hartter, and Wolfgang H. Jost. "Pramipexole Extended Release: A Novel Treatment Option in Parkinson's Disease." Parkinson's Disease 2010 (2010): 1–7. http://dx.doi.org/10.4061/2010/612619.
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Pramipexole, the most commonly prescribed dopamine agonist worldwide, meanwhile serves as a reference substance for evaluation of new drugs. Based on numerous clinical data and vast experiences, efficacy and safety profiles of this non-ergoline dopamine agonist are well characterized. Since October 2009, an extended-release formulation of pramipexole has been available for symptomatic treatment of Parkinson's disease. Pramipexole administration can be cut down from three times to once a day due to the newly developed extended-release formulation. This is considerable progress in regard to minimizing pill burden and enhancing compliance. Moreover, the 24 h continuous drug release of the once-daily extended-release formulation results in fewer fluctuations in plasma concentrations over time compared to immediate-release pramipexole, given three times daily. The present study summarizes pharmacokinetics and all essential pharmacological and clinical characteristics of the extended-release formulation. In addition, it provides all study data, available so far, with regard to transition and de-novo administration of extended-release formulation for patients with Parkinson's disease. It further compares efficacy and safety data of immediate-release pramipexole with the extended-release formulation of pramipexole.
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Merlino, Giovanni, Simone Lorenzut, Martina Sommaro, Gian Luigi Gigli, and Mariarosaria Valente. "Pharmacotherapy of Restless Legs Syndrome with Pramipexole." Clinical Medicine Insights: Therapeutics 2 (January 2010): CMT.S3580. http://dx.doi.org/10.4137/cmt.s3580.
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Restless Legs Syndrome (RLS) is one of the most common neurological diseases characterized by an urge to move the legs, often associated with unpleasant sensations relieved by movement. It is engendered by rest, and is worse in the evening or at night. Patients affected by severe RLS should be treated pharmacologically. Dopamine-agonists represent the first-line treatment for RLS symptoms. Pramipexole is a non-ergot derived dopamine agonist with a high selectivity for D2 and D3 receptors. At doses comprised between 0.125 and 0.75 mg, pramipexole improves subjective symptoms and objective signs of primary RLS even after the first administration. In addition, pramipexole seems to be safe and well tolerated. However, physicians should be aware that augmentation and compulsive behaviours might occur in their RLS patients treated with pramipexole. Further studies are needed to confirm the efficacy of pramipexole in uremic RLS and in children affected by the sleep disorder.
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Zhou, Haiyan, Shuhua Li, Hongmei Yu, Shenggang Sun, Xinhua Wan, Xiaodong Zhu, Chun-Feng Liu, et al. "Efficacy and Safety of Pramipexole Sustained Release versus Immediate Release Formulation for Nocturnal Symptoms in Chinese Patients with Advanced Parkinson’s Disease: A Pilot Study." Parkinson's Disease 2021 (March 3, 2021): 1–12. http://dx.doi.org/10.1155/2021/8834950.
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Objective. To explore the efficacy and safety of pramipexole sustained release (SR) versus pramipexole immediate release (IR) in treating nocturnal symptoms in levodopa-treated Chinese patients with advanced Parkinson’s disease (PD) and sleep disturbances. Method. SUSTAIN was an open-label, randomised, active-controlled parallel group exploratory pilot study (NCT03521635). A total of 98 patients were randomly allocated (1 : 1) to either pramipexole SR (n = 49) or pramipexole IR (n = 49) groups. The primary endpoint was a change from baseline in PD Sleep Scale 2nd version (PDSS-2) total score at 18 weeks. A reduction in score represents improvement. Secondary endpoints included Nocturnal Hypokinesia Questionnaire, Scales for Outcomes in PD Sleep Scale, Early Morning Off (EMO), Epworth Sleepiness Scale, PD Questionnaire-8, and responder rates as measured by PDSS-2 total score (<18), EMO scores (≥1 point change), Clinical Global Impression Improvement scale, and Patient Global Impression-Improvement scale. Other endpoints included motor complications (MDS-UPDRS part IV) score. Adverse events were evaluated for each group. Results. The mean pramipexole dose for both groups was 1.5 mg/day at week 18, and the mean changes in PDSS-2 total score for pramipexole SR and IR were –13.7 (95% CI –16.0 to –11.4) and –14.4 (–16.8 to –12.0) (difference of 0.7; p = 0.688 ). Change from baseline for both groups achieved the minimal clinical important difference threshold (MCID = –3.44). No significant difference was observed in change from baseline for other measures of sleep-related disturbances or responder rates. For motor complications, a greater improvement in MDS-UPDRS part IV score was observed in pramipexole SR over IR (–3.4 vs –2.3; treatment group difference: –1.1; p = 0.036 ). Both groups had comparable safety profiles. Conclusion. In Chinese patients with advanced PD and sleep disturbances, pramipexole SR and IR have similar benefits in the treatment of nocturnal symptoms and safety, and an improvement from baseline in nocturnal symptoms was observed regardless of pramipexole formulation.
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Henry, E. "Une expérience clinique du pramipexole chez 64 patients déprimés uni ou bipolaires suivis en ambulatoire." European Psychiatry 30, S2 (November 2015): S58. http://dx.doi.org/10.1016/j.eurpsy.2015.09.162.
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Du fait de l’analogie entre apathie et dépression [1,2], nous avons utilisé le pramipexole [3] chez 64 patients déprimés (39 patients présentant une dépression uni ou bipolaire, 25 patients présentant des troubles dysthymiques). Tous les patients, depuis trois mois au moins, prenaient un traitement par inhibiteur sélectif de la recapture de la sérotonine (ISRS) maintenu sans modification. Il s’agit d’une étude rétrospective portant sur quatre années d’utilisation du pramipexole La sévérité de la dépression a été cotée par le patient sur l’échelle de Hamilton 21 items et par l’investigateur sur l’échelle Montgomery and Asberg Depression Rating Scale (MADRS). Tous les patients ont été revus un à deux mois après l’introduction du pramipexole. La posologie du pramipexole a été de 1,4 mg par jour atteinte en 16 jours. Les critères d’amélioration ont été définis comme l’obtention d’un score inférieur à 10 sur l’échelle de Hamilton et un score inférieur à 10 sur l’échelle MADRS. Parmi les 25 patients présentant un trouble dysthymique, 3 patients ont été améliorés Parmi les 39 patients présentant une dépression uni- ou bipolaire, 35 ont été améliorés. L’amélioration chez ces 38 patients est survenue 10 à 15 jours après le début du traitement. Tous les patients améliorés présentaient une variation franche de l’humeur au cours de la journée avec moindre intensité de la souffrance en fin de journée. La médiane de suivi a été de 23 mois. Les nausées (5 patients) et la somnolence (6 patients) n’ont pas nécessité de modification dans la progression de la posologie. Deux patients ont présenté un épisode maniaque résolutif en 5 à 10 jours après l’arrêt du pramipexole, 1 patient a présenté des hallucinations visuelles résolutives 15 jours après l’arrêt du pramipexole et 1 patient a présenté un priapisme résolutif dès l’arrêt du pramipexole. Aucun cas d’addiction au pramipexole n’a été observé. Au total, le pramipexole semble être un traitement bien toléré et efficace chez les patients présentant une dépression dans le cadre d’un trouble uni ou bipolaire. Il ne semble pas avoir d’indication lors de troubles dysthymiques.
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Hajian, Sepideh, Mohammad Reza Rajabpoor Nikfam, and Zahra Esmayeilzad. "Comparison of the effects of pramipexole and gabapentin on the treatment of restless leg syndrome in end-stage chronic renal failure patients undergoing hemodialysis." Journal of Nephropathology 9, no. 3 (February 12, 2020): e25-e25. http://dx.doi.org/10.34172/jnp.2020.25.
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Introduction: Despite the high prevalence of restless legs syndrome (RLS) in hemodialysis patients, few studies have investigated the effect of pramipexole and gabapentin on the severity of RLS in these patients. Objectives: The study aimed to evaluate the effects of pramipexole and gabapentin on the treatment of RLS in end-stage chronic renal failure patients undergoing hemodialysis. Patients and Methods: Using the diagnostic criteria the presence of RLS was investigated in all hemodialysis patients admitted to the dialysis ward of Bu Ali Sina and Velayat hospitals in Qazvin, Iran. Out of 162 patients, 96 patients had RLS and 60 patients with moderate to severe RLS were enrolled in the study. The selected patients were randomly divided into two groups including pramipexole (0.18 mg daily) and gabapentin (100 mg daily). The two groups were treated for 4 weeks. Results: The prevalence of RLS was 59% (96 out of 162 patients). After the intervention, the severity of RLS was significantly decreased in all patients and also in each of the pramipexole and gabapentin groups (P<0.001). Moreover, after the intervention, the rate of improvement in RLS severity in the pramipexole group (16.8 ± 6.5) was significantly higher than that in the gabapentin group (13.0 ± 7.3; P=0.036). Conclusion: The findings of the study showed that the severity of RLS in hemodialysis patients undergoing 4 weeks of treatment with pramipexole or gabapentin was significantly reduced; in addition, the rate of improvement in RLS severity was higher in pramipexole group.
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Hauser, Robert A., Mark Forrest Gordon, Yoshikuni Mizuno, Werner Poewe, Paolo Barone, Anthony H. Schapira, Olivier Rascol, Catherine Debieuvre, and Mandy Fräßdorf. "Minimal Clinically Important Difference in Parkinson’s Disease as Assessed in Pivotal Trials of Pramipexole Extended Release." Parkinson's Disease 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/467131.
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Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients.Objectives. To calculate the MCID for Unified Parkinson’s Disease Rating Scale (UPDRS) scores in early Parkinson’s disease (EPD) and for UPDRS scores and “OFF” time in advanced Parkinson’s disease (APD).Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves “a little better” on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged.Results. MCIDs in EPD (pramipexole ER, pramipexole IR) for UPDRS II were −1.8 and −2.0, for UPDRS III −6.2 and −6.1, and for UPDRS II + III −8.0 and −8.1. MCIDs in APD for UPDRS II were −1.8 and −2.3, for UPDRS III −5.2 and −6.5, and for UPDRS II + III −7.1 and −8.8. MCID for “OFF” time (pramipexole ER, pramipexole IR) was −1.0 and −1.3 hours.Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.
Dissertations / Theses on the topic "Pramipexolo"
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ESPA, ELENA. "Meccanismo d'azione del Pramipexolo nella terapia della malattia di Parkinson." Doctoral thesis, Università degli Studi di Cagliari, 2015. http://hdl.handle.net/11584/266366.
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Pramipexole (PPX) is a dopamine (DA) D3 and D2 receptors agonist widely used alone or in combination with levodopa as Dopamine Replacement Therapy in Parkinson’s disease. In clinical and preclinical studies, PPX improved motor deficits, this evidence led to lowering daily dose of levodopa, delaying the motor side effects associated with its use. Recently, PPX administration has been associated to the development of addictive-like behaviors related to the DA Dysregulation Syndrome, particularly in a subpopulation of treated patients, characterized by impulsive-compulsive personality traits as well as previous addiction’s experience.
Based on these evidences, the aim of this study was twofold: first to investigate the pharmacological action of PPX, using a unilateral model of Parkinson’s disease in which 6-OHDA was injected in the medial forebrain bundle. After two weeks, we tested in primed and naive rats, the ability of three different doses of PPX (0,035; 0,1 and 0,35 mg/kg s.c.), to induce contralateral turning behavior as well c-fos expression after pretreatment of DA D1 antagonist SCH 39166. Next, we checked the ability of PPX to induce contralateral rotations after D2 (eticlopride) and D3 (S33084) DA antagonist pretreatment. In order to investigate the role of PPX (0,05 mg/kg s.c.) in behavioral sensitization, we tested its effect with S33084 pretreatment in levodopa sensitized rats.
Second, we assessed the correlation between PPX treatment, Parkinson’s disease and the onset of DA Dysregulation Syndrome on Conditioned Place Preference (CPP) paradigm. To do this, 6-OHDA was injected bilaterally in DA striatal terminals, in three different strains of rat: the addiction prone Lewis (LEW), the addiction resistant Fisher 344 (F344) inbred strains, and the Sprague Dawley (SD) outbred strain. Furthermore, to test its rewarding properties, PPX was directly infused in the nucleus accumbens shell (NAc), a DA mesolimbic region known to be involved in the rewarding effects of drugs of abuse, in healthy rats belonging to the above mentioned strains.
We discovered that in primed rats, PPX (0,35 mg/kg s.c.) induced turning behavior that was increased by SCH 39166 pretreatment (0,1 mg/kg s.c.). No effect was seen in naive rats both for turning behavior and c-fos expression. D2 receptors antagonist eticlopride (0,1 mg/kg s.c.) reduced PPX-induced turning behavior more than D3 receptors antagonist S33084 (0,5 mg/kg s.c.), also a previous levodopa sensitization increased PPX-induced turning behavior on its first administration. This suggests that PPX’s action could be related to D2 stimulation, and it seems to require a previous D1/D2 stimulation to observe a behavioral outcome.
PPX (1 mg/kg s.c.) was able to induce a significant CPP in SD and LEW lesioned rats but not in F344 and control rats, and the persistence of preference was stronger in LEW than in SD rats. When injected into the NAc shell, PPX (5 μg/0.5 μl) induced CPP in all rat strains, but the persistence of its effect was more strong in LEW compared to SD and F344 rats. These results suggest that the parkinsonian state might be more sensitive to the rewarding properties of PPX, which do not seem entirely influenced by phenotype.
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Johnson, Patrick S. "Behavioral Mechanisms of Pramipexole-Induced Impulsivity: Discrimination Processes Underlying Decision-Making." DigitalCommons@USU, 2012. https://digitalcommons.usu.edu/etd/1259.
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Faced with an intertemporal choice, an organism that chooses a “smaller-sooner” reinforcer over a “larger-later” reinforcer is said to behave impulsively. Individual differences in intertemporal choice are effectively modeled by generalized matching law and delay discounting equations that incorporate parameters corresponding to behavioral processes such as sensitivity to reinforcer amount or delay. By simulating changes in these processes and identifying conditions under which impulsive choice is likely to result, researchers are in a position to anticipate and examine potential behavioral mechanisms underlying clinical instances of impulsivity. Pramipexole, a dopamine agonist medication, is associated with reports of impulsive behavior in populations prescribed the drug, as well as in experimental subjects administered the compound prior to intertemporal choice sessions, although the latter findings are mixed. The present set of experiments was designed (a) to systematically replicate conditions under which pramipexole increased impulsive choice, but also nonspecifically disrupted behavior, and (b) to elucidate behavioral mechanisms of pramipexole-induced impulsivity in rats. In Chapter 2, a behavioral task used previously by researchers reporting a nonspecific effect of pramipexole was modified to include procedural controls common in the intertemporal choice literature (centering response, no-delay sessions). In accord with previous findings, acute pramipexole nonspecifically disrupted choice behavior, while chronic pramipexole partially remediated elements of the disruption (i.e., decrease in initial-block choice). In Chapter 3, three experiments targeted behavioral processes critical for intertemporal choice. Experiment 1 evaluated the acute and chronic effects of pramipexole on rats’ sensitivity to relative reinforcer delays in a concurrent-chains procedure. Contrary to the predicted effect, the drug decreased this measure, indicating the possibility of impaired stimulus control. Experiments 2 and 3 assessed the drug effect on discrimination of response-reinforcer contingencies and of reinforcer amounts, respectively, and revealed deficits in accuracy of similar magnitude across both preparations. Collectively, the results of these experiments suggest that previous findings of pramipexole-induced impulsivity and nonspecific disruption of behavior can be explained as impairments in discrimination processes required for intertemporal choice. Although the generality of the present findings may be limited to experimental settings with nonhumans, they demonstrate the utility of quantitatively modeling impulsivity.
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Lieberknecht, Vicente. "Efeito neuroprotetor do pramipexol, agonista de receptores dopaminérgicos D2/D3, nos modelos de esclerose múltipla e de depressão." reponame:Repositório Institucional da UFSC, 2016. https://repositorio.ufsc.br/xmlui/handle/123456789/175822.
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Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Neurociências, Florianópolis, 2016.Made available in DSpace on 2017-05-23T04:11:56Z (GMT). No. of bitstreams: 1 345666.pdf: 3373156 bytes, checksum: 7027682a29338f16909d04b013f2baf4 (MD5) Previous issue date: 2016
As doenças de Parkinson, de Alzheimer e esclerose múltipla (EM), bem como os transtornos de humor, como a depressão, apresentam componentes inflamatórios. As células do sistema imune possuem 5 receptores que respondem ao neurotransmissor dopamina, os quais modulam diferentemente a inflamação. Assim, é esperado que o pramipexol (PPX), um agonista de receptores dopaminérgicos (D2/D3), tenha efeito imunomodulatório. Para testar essa hipótese foram utilizados dois modelos que causam neuroinflamação: a) a encefalomielite autoimune experimental (EAE), modelo de esclerose múltipla e b) a administração periférica de lipopolissacarídeo (LPS), modelo de transtorno depressivo maior. A EAE foi induzida em camundongos C57BL/6 através da administração do peptídeo 35-55 da glicoproteína de mielina oligodendroglial e o PPX (0,1 e 1 mg/kg/dia) foi administrado pela via intraperitoneal por 40 dias. A dose de 1 mg/kg inibiu completamente o surgimento dos sinais motores induzidos pela EAE, além de prevenir a desmielinização na medula espinhal. Além disso, o PPX teve um forte efeito anti-inflamatório, confirmado através da redução da infiltração de células inflamatórias, da ativação astroglial na medula espinhal, e da redução nos níveis de IL-17 nos linfonodos. Além disto, o PPX reverteu várias alterações induzidas pela EAE na medula espinhal e no estriado, incluindo a redução nos níveis de a-sinucleína, o aumento nos níveis de parkina, alteração na enzima glutationa peroxidase e a produção de espécies reativas de oxigênio. Em conjunto os dados sugerem que o PPX deve ser estudado como um possível agente farmacológico para tratar a EM. No modelo de depressão induzida por inflamação periférica através da injeção de LPS em camundongos Swiss, o PPX (1 mg/kg), foi administrado por 7 dias por via intraperitoneal. Uma hora após a última aplicação de PPX, injetou-se LPS (0,1 mg/kg) via intraperitoneal, 24 h depois foi dado início aos testes comportamentais. O LPS induziu comportamento tipo-depressivo no teste do nado forçado e no splash test, sem alterar a locomoção no teste do campo aberto. Também foi observado o aumento de Interleucina-1ß e adutos de 3-nitrotirosina no hipocampo dos animais tratados com LPS. Todos estes parâmetros foram revertidos pelo PPX, indicando que o PPX é capaz diminuir os eventos inflamatórios que podem estar associados ao comportamento tipo-depressivo. Os antagonistas de receptores dopaminérgicos, haloperidol e sulpirida, não reverteram o efeito tipo-antidepressivo do PPX, indicando que a atuação do PPX parece não ser mediada por estes receptores. Em conjunto, os dados sugerem que o PPX é capaz de causar uma forte diminuição em processos inflamatórios, tanto no modelo de EAE como no modelo de depressão, o que pode ser o mecanismo responsável por sua ação. Porém, mais estudos são necessários para confirmar esta hipótese.
Abstract : Neurologic diseases as Parkinson's, Alzheimer's and multiple sclerosis (MS) as well as mood disorders, like major depression, present inflammatory components. Immune cells express 5 different dopamine receptors, which are known to modulate inflammation. In this context, it is expected that pramipexole (PPX), a dopamine D2/D3 receptor agonist, would have an immunomodulatory effect. To evaluate this hypothesis two neuroinflammatory disease models were used, the experimental autoimmune encephalomyelitis (EAE), a mice model of MS, and the peripheral administration of lipopolysaccharide (LPS), a mice model of major depression disorder (MDD). EAE was induced in C57Bl/6 mice by the injection of the 35-55 peptide of myelin oligodendroglial glycoprotein. PPX (0.1 and 1 mg/kg) was administered by intraperitoneal route for 40 days. The dose of 1 mg/kg of PPX completely abolished motor impairment induced by EAE, and prevented medular demyelination. Besides, PPX had a marked anti-inflammatory effect, which was observed by reduction of inflammatory cells infiltration, astroglyal activation, and by decreasing IL-17 levels in lymph nodes. Besides, PPX reversed several alterations in the spinal cord and striatum induced by EAE, inclunding reduction in a-synuclein levels, enhancement of parkin levels, alteration in glutathione peroxidase activity and reactive oxygen species production. Together, these results suggest that PPX can be studied as a potential drug for MS treatment. In the MDD model induced by peripheral inflammation induced with the bacterial lipopolysacchired (LPS) administration in Swiss mice, PPX (1 mg/kg) was administered for 7 days by intraperitoneal route. One hour after the last PPX injection, LPS (0.1 mg/kg) was administered intraperitoneally, and 24 h later behavioral analysis were performed. LPS induced depressive-like behavior in the forced swimming test and splash test, without locomotor alterations in the open field test. It was also observed enhancement of Interleukin-1ß and 3-nitrotyrosin protein adducts in mice hippocampus of LPS treated animals. PPX reversed all these alterations, indicating that PPX can prevent the inflammatory events related to the depressive-like behavior. Interestingly, the dopamine receptor antagonists, haloperidol and sulpiride, did not reverse the PPX antidepressant-like effect in the forced swimming test, indicating that PPX effect seems to be unrelated by these receptors. Together, these results suggest that PPX present a marked antiinflammatory action, in both EAE and LPS models, suggesting that this could be the mechanism of action of PPX. Nevertheless, further studies are required to confirm this hypothesis.
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Silindir, Gunay Mine. "The Preparation of theragnostic immunoliposomes/immunoniosomes and therapy of Parkinson's disease." Thesis, Tours, 2016. http://www.theses.fr/2016TOUR3807/document.
Full textAbstract:
La maladie de Parkinson (MP) provient de la dégénérescence des cellules du locus nigerproduisant de la dopamine. La barrière hémato-encéphalique (BHE) est un véritable obstacle pour le traitement de la MP car elle empêche ou réduit le passage d’un grand nombre de substances pharmacologiques vers le cerveau. L’encapsulation de ces substances dans des liposomes ou des niosomes avant leur libération intra-cérébrale représente une alternative de choix en raison de la biocompatibilité, la biofragmentation, la non-toxicité et les capacités de ciblage de ces systèmes. A l’heure actuelle le traitement de la MP reste un défi, malgré l’existence de nombreux projets de recherche dans ce domaine. Notre hypothèse est que l’administration de pramipexoleencapsulé dans des liposomes et/ou des niosomes pourrait représenter une approche thérapeutique pertinente. Dans le cadre de la thèse, la caractérisation et la cinétique de diffusion des liposomes et niosomescontenant du pramipexole ont été réalisées. La validation de différentes formulations a été réalisée sur un modèle de BHE constitué de co-cultures cellulaires. Les effets du pramipexoleencapsulé dans des liposomes ou desniosomesont ensuite été étudiés dans un modèle de MP chez le rat obtenu par lésion de la voie dopaminergique nigro-striée à l’aide de 6-hydroxydopamine (6-OHDA). Pour cela, nous avons évalué le comportement rotatoire induit par l’amphétamine et l’expression du transporteur de la dopamine (DAT) par autoradiographie quantitative chez des animaux lésés traités ou non par les nanocapsules. Toutes les formulations que nous avons réalisées ont montré une capacité d’encapsulation d’environ 10% pour une taille de 100 nm, avec une cinétique de dispersion compatible avec une utilisation in vivo. Dans notre modèle de co-culture cellulaire, nous avons déterminé que nos formulations permettent le franchissement de la BHE. Chez les animaux lésés à la 6-OHDA, la quantification du DAT indique que l’administration de pramipexole réduit l’intensité de la lésion, que la substance soit administrée seule ou encapsulée dans des niosomes. Ces travaux montrent l’intérêt potentiel de l’administration de principe actif encapsulé pour le traitement de la MP, et devront être poursuivis afin d’optimiser cette approche thérapeutique, notamment au niveau des dosesParkinson’s Disease (PD) is degeneration of dopamine producing cells in substantia nigra. Blood-brain barrier (BBB) is a strong obstacle in PD therapy. More penetration and accumulation in the target tissue can be obtained by preventing RES uptake via “stealth effect”. Liposomes and niosomes are the promising systems for being biodegredable, bioavailable, non-toxic and targetable. Although CNS disorders are the first to endorse at their research in the diagnosis and therapy with several framework projects in Europe and over the world, there is still a huge gap in CNS drug delivery and the success of PD therapy. Although different studies have performed with pramipexole, evaluation of penetration and antiparkinsonian effect of pramipexole encapsulated liposomes and niosomes has never been studied before. Among this thesis, nanosized, polyethylene glycol (PEG) coated, neutral and positively charged, pramipexole encapsulated liposomes and noisomes were formulated, characterized and release kinetics of the systems were evaluated. In vitro penetration of all formulations was evaluated in BBB cell co-culture model. Therapeutic efficacy of neutral, pramipexole encapsulated liposomes and niosomes were evaluated in 6-hydroxydopamine (6-OHDA) lesioned rats by rotometer test and autoradiography. All formulations have approximately 10% encapsulation efficiency, around 100 nm particle sizes and fitted to first-order release kinetics. All formulations were found BBB permeable at in vitro cell culture studies. Nanosized, neutral niosomes designated similar but slightly better effect than pramipexole solution in autoradiograhy studies in 6-OHDA lesioned rats. This pramipexole dose is approximately 9 times lesser doses applied with conventional pramipexole tablets for humans in Neurology clinics. Nanosized, pramipexole encapsulated, neutral niosomes showed potential PD therapeutic effect in PD animal model depending on non-ionic surfactant properties of niosomes
Uzm. Ecz. Mine Silindir Gunay, Parkinson Hastalığı’nın Teşhis ve Tedavisi İçin Kullanılacak Nanoboyutlu Teragnostik İmmünolipozom/İmmunoniozomlar Üzerine İn Vitro İn Vivo Çalışmalar, Hacettepe Üniversitesi – François Rabelais de Tours University, Sağlık Bilimleri Enstitüsü, Radyofarmasi Programı, UMR Inserm U 930, Ekip 3, Moleküler Görüntüleme ve Beyin Programı, Doktora Tezi, Ankara-Tours, 2016. Parkinson Hastalığı (PH) substantia nigra’daki dopamin üreten hücrelerin dejenerasyonundan kaynaklanmaktadır. Kan-beyin bariyeri (KBB) PH’nın tedavisinin önünde kuvvetli bir engeldir. Hedef dokudaki yüksek penetrasyon ve tutulum “stealth etki” ile RES tutulumunun engellenmesi ile sağlanabilir. Lipozom ve niozomlar biyoparçalanırlıkları, biyouyumlulukları, non-toksik ve hedeflendirilebilir olmaları nedeniyle en çok tercih edilen sistemlerdendir. Santral sinir sistemi hastalıklarının araştırılması Avrupa ve tüm dünyada yapılan pekçok çerçeve projelerinde ilk sırada olmasına rağmen, halen beyne ilaç taşınması ve PH’nin tedavi başarısı konusunda büyük boşluklar bulunmaktadır. Pramipeksol ile pek çok çalışma yapılmasına karşılık, bizim çalışmamız pramipeksol enkapsüle edilmiş lipozom ve niozomların beyin penetrasyonunun ve antiparkinson etkisinin değerlendirilmesi konusunda yenidir. Tez kapsamında, nanoboyutlu, PEG kaplı, nötral ve pozitif yüklü lipozom ve niozomların formüle edilmiş, karakterizasyon ve salım kinetikleri değerlendirilmiştir. Tüm formülasyonların KBB geçirgenliği, hücre KBB ko-kültürü çalışmalarında incelenmiştir. Nötral, pramipeksol enkapsüle edilen lipozom ve niozomların tedavi etkinliği in vivo olarak 6-hidroksidopamin (6-OHDA) ile lezyon yapılarak PH modeli oluşturulan sıçanlarda rotametre ve otoradyografi çalışmaları ile incelenmiştir. Tüm formülasyonlar yaklaşık %10 enkapsülasyon etkinliği ve 100 nm civarında partikül boyutu dağılımı ve birinci derece salım kinetiği göstermiştir. Hücre kültürü çalışmalarında, tüm formülasyonların KBB’nden penetre olabildiği saptamıştır. 6-OHDA lezyonlu sıçanlarda Parkinson hastalığının tedavisinde nanoboyutlu, nötral, pramipeksol enkapsüle edilen niozomlar, aynı dozdaki pramipeksol çözeltisi ile benzer hatta biraz daha iyi sonuçlar göstermiştir. Bu doz Nöroloji kliniklerinde Parkinson tedavisinde rutin olarak kullanılan konvansiyonel pramipeksol tabletlerindeki dozun yaklaşık olarak 9 kat düşük dozlarıdır. Nanoboyutlu, pramipeksol enkapsüle edilen, nötral niozomlar, niozomların non-iyonik sürfaktan özellikleri nedeniyle PH modeli sıçanlarda potansiyel bir antiparkinson terapötik etki göstermiştir
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Loiodice, Simon. "Altérations du système de récompense dans la maladie de Parkinson : relation entre comportement et signatures moléculaires. : Neuropsychopharmacologie." Thesis, Clermont-Ferrand 1, 2016. http://www.theses.fr/2016CLF1MM10.
Full textAbstract:
Dans la maladie de Parkinson (MP), la perte progressive des neurones dopaminergiques (DA) touche principalement la substantia nigra pars compacta (SNc). Les symptômes moteurs sont classiquement gérés par une thérapie dopaminergique de remplacement (TDR). Conjointement à la levodopa, l’utilisation d’agonistes dopaminergiques permet de prévenir les complications motrices mais peut être associée à des troubles du système de récompense. Jusqu’à 14% des patients parkinsoniens sous TRD peuvent souffrir de comportement « addiction-like » tels que le pari pathologique, l’hypersexualité ou une prise compulsive de la médication DA. A ce jour la seule solution thérapeutique consiste à diminuer la TRD ce qui détériore les symptômes moteurs. Les neuroadaptations conduisant à ces troubles du système de récompense demeurent mal comprises. Nous proposons un travail dans lequel nous avons évalué les propriétés appétitives de l’agoniste D2/D3 pramipexole (ppx) après une exposition chronique à la L-dopa dans un modèle de rat parkinsonien alpha-synucléine. Dans une première étude, nous avons évalué l’effet d’une stimulation répétée des récepteurs DA sur la sensibilisation du système de récompense en contexte parkinsonien. Nos résultats montrent un effet récompensant du ppx après administrations chronique de L-dopa et perte DA nigrostriatal induite par surexpression de l’alpha-synucléine. Aucune modification transcriptionnelle n’a été observée pour les récepteurs DA. Cependant, nous avons identifié une association entre lésion/traitement pharmacologique et des changements transcriptionnels potentiellement liés à un contexte d’addiction aux psychostimulants. Cette étude fournit des preuves suggérant fortement la lésion parkinsonienne et la thérapie L-dopa comme des facteurs conjointement impliqués dans le remodelage cérébral sous-tendant une préférence de place conditionnée pour le ppx. Les données moléculaires et pharmacologiques générées ont suggéré un rôle clé de la voie glutamatergique dans cette réponse comportementale. Ce résultat est cohérent avec la littérature décrivant un déséquilibre glutamatergique striatal dans les contextes d’addiction aux psychostimulants et de complications motrices associées à la MP. Ainsi, nous avons conçu une deuxième étude visant à investiguer plus avant le potentiel thérapeutique d’une inhibition des récepteurs glutamatergiques. Une lésion bilatérale de la SNc a été réalisée par surexpression de la protéine alpha-synucléine au moyen d’un vecteur AAV. Suite à cette lésion, un traitement chronique à la L-dopa a été réalisé. L’effet de l’antagoniste des récepteurs mGluR5 (metabotropic glutamate receptor 5) MPEP sur les propriétés renforçatrices du ppx a été évalué dans un paradigme de préférence de place conditionnée. Enfin, une analyse des changements d’expression de protéines d’intérêt a été réalisé afin d’associer changements comportementaux drogue/lésion induits et paramètres moléculaires. L’acquisition et l’expression de la préférence de place ppx-induite a été abolie par le MPEP. De plus, nous avons identifié des réseaux neuraux et des modifications d’expression protéiques sous-tendant les plasticités striatales associées à la réponse comportementale. L’ensemble de ces travaux apporte de nouvelles idées sur le contexte physiopathologique associé aux troubles du système de récompense dans la MP. Des données moléculaires et pharmacologiques convergentes suggèrent fortement le mGluR5 comme une cible thérapeutique prometteuseIn Parkinson’s Disease (PD), the progressive dopaminergic (DA) cell loss mainly affects the substantia nigra pars compacta (SNc). The motor symptoms are classically managed by DA replacement therapies (DRT). Although adding DA agonists to levodopa treatment may contribute to prevent motor complications, it may be associated with drug‑induced changes in reward related pathways. Up to 14% of PD patients under DRT may suffer from ‘addiction‑like’ behavior such as pathological gambling, hypersexuality or DA medication‑induced substance abuse. To date, the only therapeutic answer consists in lowering the DA medications which deteriorates the motor symptoms. Neuroadaptations leading to reward bias in PD patients under DRT are still poorly understood. To address this challenge, we propose a work in which we have assessed the rewarding effect of the D2/D3 agonist pramipexole (ppx) after chronic exposure to L‑dopa in an alpha-synuclein PD rat model. In a first study, we assessed the effect of repeated DA receptors stimulations on sensitization of the reward system in a parkinsonian context. Our findings demonstrated that ppx had a rewarding effect after chronic L-dopa administrations and alpha-synuclein-mediated nigral loss. No transcriptional changes within DA receptors were highlighted. However, we identified an association between the main drug or lesion and transcriptional changes which were potentially related to the context of psychostimulant addiction. This study provides evidences strongly suggesting that PD-like lesion and L-dopa therapy were concomitant factors involved in striatal remodeling underlying the ppx-induced place preference. Molecular and pharmacological data suggested a key involvement ofthe glutamatergic pathway in this behavioral outcome. These data were consistent with literature describing major striatal glutamate imbalance as a common feature of drug addiction and Parkinson’s disease physiopathological contexts. Hence, we designed a second study aiming to further investigate the therapeutic potential of glutamatergic receptors inhibition. A bilateral lesion of the SNc was performed in the rat using AAV-mediated overexpression of the alpha-synuclein. This lesion was followed by chronic L-dopa administrations. Then, the effect of the metabotropic glutamate receptor 5 (mGluR5) antagonist MPEP on ppx reinforcing properties was assessed in a place conditioning paradigm. Finally, analysis at the protein level was conducted to associate drug and lesion induced behavioral changes to molecular endpoints. Acquisition and expression of the ppx-induced place preference was abolished by the MPEP. Furthermore, we identified neural networks and protein changes underlying the striatal remodeling associated with the behavioral outcome. All this work provides new insights into the physiopathological context associated to the PD/DRT related reward bias. Convergent molecular and pharmacological data strongly suggest mGluR5 as a promising therapeutic target
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Millot, Mathilde. "Implication de la sérotonine dans l'expression de troubles moteurs et neuropsycho-comportementaux dans la maladie de Parkison." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1100.
Full textAbstract:
La maladie de Parkinson (MP) se caractérise par une dégénérescence progressive et irréversible des neurones dopaminergiques de la substance noire induisant une perte de dopamine (DA) dans les structures cibles. Lorsque cette perte DA se situe entre 60 % et 80 %, les patients présentent des symptômes moteurs (rigidité, tremblement, akinésie) et non-moteurs très variés (dépression, anxiété, apathie). Ces derniers apparaissent avant et/ou en même temps que les symptômes moteurs. La dopathérapie permet de contrecarrer certains symptômes, mais tous ne sont pas sensibles à cette médication. Parallèlement à la dégénérescence DA, le système sérotoninergique (5-HT) serait aussi altéré de façon précoce dans la maladie. Cette dégénérescence est liée par l’expression de symptômes moteurs et non-moteurs. Néanmoins, aucun lien causal n’a été mis en évidence entre cette lésion 5-HT et la symptomatologie parkinsonienne. Ainsi, il était primordial de déterminer le rôle de la 5-HT dans 1) l’expression des troubles moteurs et non-moteurs 2) dans la réponse au traitement sérotoninergique et dopaminergique. Nous avons utilisé un nouveau modèle animal primate ayant une lésion 5-HT (via la MDMA) puis une lésion DA (via le MPTP). Ce modèle nous permet de mettre en évidence l’impact d’une lésion 5-HT précoce dans la symptomatologie. Des approches comportementales, pharmacologiques, d’imagerie et de neuroanatomie ont été utilisées. La lésion 5-HT a induit un trouble anxieux chez les animaux lésés à la MDMA, qui ne sont pas contrecarrer avec un traitement sérotoninergique (antidépresseur). Cette lésion a également induit une sévérité et une progression plus rapide des symptômes moteurs induits par la lésion DAParkinson’s disease (PD) is characterized by a progressive and irreversible degeneration of dopaminergic (DA) neurons localized in the substantia nigra, leading to a loss of dopamine within the target structures. When the loss of DA reaches 60 to 80 %, PD patients develop a wide range of motor (rigidity, tremor, akinesia fro example) and non-motor (depression, anxiety, apathy for example) symptoms. Dopatherapy allows the reduction of symptoms expression. But some motor and non-motor symptoms are not counteracted by those DA drugs. In addition to DA degeneration, patients present an early serotonergic (5-HT) lesion. This lesion is linked to the severity of some motor and non-motor symptoms. However, there is no causal link established between 5-HT lesion and parkinsonian symptoms. Therefore, it was essential to determine the role of 5-HT 1) in the expression of motor and non-motor symptoms 2) and in the response of DA and 5-HT treatments. For that, we used a new monkey model of PD, exhibiting a 5-HT lesion (with MDMA ‘”ecstasy”)) followed by a DA lesion (with MPTP). This model allowed us to evaluate the impact of an early 5-HT lesion on parkinsonian symptoms. We used different approaches: PET imaging, pharmacology, behavioral and neuroanatomy. The MDMA-driven early 5-HT lesion induced an anxious-like behavior on MDMA treatedmonkeys. This behavioral modification was not counteracted by 5-HT drugs (antidepressant). This MDMA lesion has also increased the severity and the progression of parkinsonian symptoms induced by DA lesion with MPTP
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Magnard, Robin. "Mécanismes physiopathologiques des comportements impulsifs associés à la maladie de Parkinson : approches expérimentales chez le rat." Thesis, Université Grenoble Alpes (ComUE), 2019. http://www.theses.fr/2019GREAV006/document.
Full textAbstract:
Au-delà des symptômes moteurs, la maladie de Parkinson (MP) est également caractérisée par une myriade de symptômes neuropsychiatriques allant de l’apathie et la dépression aux troubles du contrôle des impulsions (TCI). Les TCI représentent un groupe d’addictions comportementales incluant le jeu pathologique, l’hypersexualité et les achats faits de manière compulsive. Observés chez 10 à 14 % des patients parkinsoniens sous traitement dopaminergique, ils affectent fortement leur qualité de vie. L’impulsivité cognitive reflétant notamment l’incapacité à tolérer les délais de renforcements, est au cœur des TCI. En effet, différentes études suggèrent que cette impulsivité serait exacerbée dans la MP et sous traitements dopaminergiques. Cependant, les mécanismes sous-tendant les TCI dans la MP demeurent méconnus, et la contribution respective de la lésion, du traitement dopaminergique, et de certains facteurs de vulnérabilité reste à déterminer. De plus, l’impulsivité d’attente, une autre forme de déficit d’inhibition qui peut conduire au développement de comportements compulsifs, a été peu étudiée dans le cadre des TCI.L’objectif de ce projet de thèse a été d’évaluer l’influence d’une dénervation dopaminergique de la voie nigrostriée, avec ou sans adjonction d’agoniste dopaminergique, sur le développement d’impulsivité. Pour cela, nous avons utilisé un modèle lésionnel des troubles non-moteurs de la MP. Ces rats ont reçu une injection bilatérale de neurotoxine 6-OHDA dans la SNc, afin d’induire une dénervation sélective, bilatérale et partielle du striatum dorsal. Ils ont ensuite été traités avec du pramipexole, un agoniste des récepteurs D2/3, connu pour favoriser le développement de TCI chez les patients parkinsoniens. Les tâches d’intolérance au délai et de réaction en série à 5 choix (5-CSRTT) ont été utilisées pour évaluer respectivement l’impulsivité cognitive et l’impulsivité d’attente. Dans le premier paradigme, les rats doivent appuyer sur un levier pour choisir entre une petite récompense immédiate, ou une plus grosse récompense, avec un un délai. Dans le second paradigme, ils doivent inhiber l’émission d’une réponse motrice jusqu’à l’apparition d’un stimulus lumineux. Le traitement chronique au pramipexole augmente considérablement les choix impulsifs effectués dans la tâche d’intolérance au délai, mais seulement chez les rats non lésés. En effet, la lésion dopaminergique seule ou avec le traitement ne favorise pas les comportements impulsifs. Dans la tâche de 5-CSRTT, le pramipexole semble également promouvoir l’émission de réponses prématurées (effet pro-impulsif), lorsque l’intervalle inter-essais est constant. Cependant, lorsque cet intervalle augmente, le pramipexole provoque à l’inverse une diminution des réponses prématurées (effet anti-impulsif). Cette modulation d’impulsivité étant seulement observée chez les rats hautement impulsifs, ceci suggère qu’un endophénotype impulsif puisse être un facteur de vulnérabilité à l’effet iatrogène du pramipexole.A l’échelle neuronale, ce traitement favorise la surexpression des ARNm codants pour les récepteurs dopaminergiques D2 dans le striatum et y modifie la connectivité glutamatergique telle qu’observée en microscopie électronique. De plus, nous avons observé une suractivation de la voie mTORC1 dans le noyau accumbens, comme déjà constaté dans les processus addictifs. Afin d’apporter un lien causal à cette étude, nous avons bloqué l’activité de la voie mTORC1 par un inhibiteur spécifique, la rapamycine, chez des rats traités au pramipexole. Etonnamment, cette combinaison accentue fortement l’intolérance au délai, alors que la rapamycine seule ne provoque aucun effet notable. Ceci pourrait s’expliquer par une cinétique d’activation et d’inhibition complexe de cette voie. L’ensemble de ces résultats suggère que l’impulsivité observée dans la MP serait causée par une action iatrogène du pramipexole via une activation anormale de la voie mTORC1 dans le noyau accumbensBeyond motor symptoms, Parkinson’s disease (PD) is also characterized by a plethora of neuropsychiatric deficits, ranging from apathy and depression to Impulse control disorders (ICDs). ICDs represent a complex group of behavioral addictions including gambling disorders, hypersexuality and compulsive shopping, displayed by 10 to 14% of PD patients under dopamine replacement therapies, whose quality of life is greatly diminished. Importantly, cognitive impulsivity reflecting in particular, an inability to tolerate delays to reinforcements, appears as a core symptom of ICDs. Indeed, recent evidence suggested that this kind of impulsivity would be exacerbated in PD and under treatment by dopaminergic D2/3 receptor agonists. However, the mechanisms underlying ICDs in PD remain unknown and the respective contribution of dopamine lesion and treatment, combined with factors of vulnerability, remain to be determined. Moreover, waiting impulsivity, another form of behavioral inhibition which may lead to compulsive behaviors, has been poorly investigated in the framework of ICDs.In this thesis project, using a lesional rodent model of non-motor symptoms of PD, we addressed the question of whether denervation of the dopaminergic nigrostriatal system would promote the development of impulsivity when combined with dopamine agonist treatments. Rats were bilaterally injected in the SNc with the neurotoxin 6-OHDA to induce selective and partial denervation of the dorsal striatum. We then treated them with the dopamine D2/3 receptor agonist, pramipexole, a medication known to favor the development of ICDs in PD patients. Two different tasks were used to measure cognitive and motor impulsivity: the delay discounting task (DDT) and the 5-choice serial reaction time task (5-CSRTT) respectively. In the former, rats have to press a lever and choose between a smaller, but immediate reward and a larger, but delayed reward. For the latter, they have to wait for a stimulus light to come on. In the DDT, chronic administration of pramipexole treatment only increased impulsive choices in non-lesioned rats. Indeed, the dopaminergic lesion by itself, or in adjunction with the treatment, did not increase impulsivity. In the 5-CSRTT, pramipexole progressively increased premature responses, reflecting a pro-impulsive effect when the inter-trial interval is constant. However, when the interval was increased, pramipexole reduced the premature responses, exhibiting an anti-impulsive effect. Interestingly, this modulation of motor impulsivity was only observed in rats with a high level of impulsivity, suggesting that an impulsive endophenotype might be an important factor of vulnerability to the iatrogenic effects of pramipexole.The effect of this treatment was then investigated at a cellular level. It promotes overexpression of the dopamine D2 receptor mRNA within the striatum, and seems to alter glutamatergic synaptic connectivity suggested by electron microscopy. Moreover, we showed that the mammalian target of rapamycin complex 1 (mTORC1) pathway is lastingly over-activated in the nucleus accumbens, as already observed in drug addictions. In an attempt to make a causal link between this pathway and the behavioral changes, we treated rats with pramipexole and rapamycine, a specific inhibitor of this pathway. Surprisingly, this combination accentuated impulsivity even more, whereas rapamycine by itself did not promote impulsivity. This effect may be explained by the complexity of the kinetics of activation and inhibition of mTORC1 pathway.Taken together, these results suggest that impulsivity in PD may be triggered by an iatrogenic effect of the dopaminergic pramipexole treatment through an abnormal activation of the mTORC1 pathway within the nucleus accumbens
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Maurer, Lukas [Verfasser], and Günter [Akademischer Betreuer] Höglinger. "Effekte einer Langzeit-Therapie mit Pramipexol oder Levodopa auf die [123I]FP-CIT SPECT in einem Mausmodell der Parkinson-Krankheit / Lukas Maurer. Betreuer: Günter Höglinger." Marburg : Philipps-Universität Marburg, 2015. http://d-nb.info/1068315458/34.
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Hermanns, Guido [Verfasser], and Günter U. [Akademischer Betreuer] Höglinger. "Effekte einer Langzeit-Therapie mit Pramipexol oder Levodopa auf das nicht-motorische Verhalten im 6-Hydroxydopamin-Mausmodell des idiopathischen Parkinson-Syndroms / Guido Hermanns ; Betreuer: Günter U. Höglinger." Marburg : Philipps-Universität Marburg, 2018. http://d-nb.info/1166314138/34.
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Richter, Johann Sebastian [Verfasser], Christine [Akademischer Betreuer] Stadelmann-Nessler, David [Akademischer Betreuer] Liebetanz, and Martin Prof [Akademischer Betreuer] Oppermann. "The effect of dopamine and its agonist pramipexole on oligodendrocytes in culture and in the cuprizone mouse model / Johann Sebastian Richter. Gutachter: David Liebetanz ; Martin Prof Oppermann. Betreuer: Christine Stadelmann-Nessler." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://d-nb.info/1047932180/34.
Full textBooks on the topic "Pramipexolo"
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Blokdijk, G. J. Pramipexole Dihydrochloride; Complete Self-Assessment Guide. Createspace Independent Publishing Platform, 2018.
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Mahon, Katie, Manuela Russo, and M. Mercedes Perez-Rodriguez. Cognitive Enhancement in Bipolar Disorder. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190214401.003.0011.
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Neurocognitive deficits are acknowledged as integral features of bipolar disorder (BD) and are known to contribute to the compromised level of functioning in individuals with BD. This chapter provides an overview of the current state of cognitive enhancement in BD. Few pharmacological agents have been investigated with regard to their potential for pro-cognitive effects in BD. Dopaminergic agents (pramipexole) and stimulants (modafinil, armodafinil, and amphetamine) as adjunctive treatment in BD appear to be promising cognitive enhancers, and there are few ongoing randomized clinical trials targeting both cognitive dysfunctions and clinical symptomatology in BD. Glutamatergic agents (d-cycloserine) may hold promise as potential cognitive enhancing agents in BD; however, as for dopaminergic agents and stimulants, no conclusive data exist. Larger samples and longer follow-up are needed to obtain a deep understanding of the efficacy and safety of these compounds and their role in the neurobiological mechanisms underpinning cognition in BD.
Book chapters on the topic "Pramipexolo"
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McAllister-Williams, R. Hamish, Daniel Bertrand, Hans Rollema, Raymond S. Hurst, Linda P. Spear, Tim C. Kirkham, Thomas Steckler, et al. "Pramipexole." In Encyclopedia of Psychopharmacology, 1054. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_1790.
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Benkert, Otto, Ion Anghelescu, Christoph Fehr, Gerhard Gründer, Philip Heiser, Christoph Hiemke, Christian Lange-Asschenfeldt, et al. "Pramipexol." In Pocket Guide Psychopharmaka von A bis Z, 200–201. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-642-01910-4_90.
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Peter, Helga. "Pramipexol." In Springer Reference Medizin, 1. Berlin, Heidelberg: Springer Berlin Heidelberg, 2020. http://dx.doi.org/10.1007/978-3-642-54672-3_770-1.
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Konaka, Kuni, and Hideki Mochizuki. "Pramipexole for Treating Parkinson’s Disease." In NeuroPsychopharmacotherapy, 1–8. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-319-56015-1_233-1.
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Konaka, Kuni, and Hideki Mochizuki. "Pramipexole for Treating Parkinson’s Disease." In NeuroPsychopharmacotherapy, 3277–84. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-62059-2_233.
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Blum, Austin W., and Jon E. Grant. "Uncontrollable Urges to Gamble Following Treatment with Pramipexole (Mirapex)." In Comorbid Sleep and Psychiatric Disorders, 201–7. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-11772-6_18.
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Reichmann, H., P. Odin, H. M. Brecht, J. Köster, and P. H. Kraus. "Changing dopamine agonist treatment in Parkinson’s disease: experiences with switching to pramipexole." In Oxidative Stress and Neuroprotection, 17–25. Vienna: Springer Vienna, 2006. http://dx.doi.org/10.1007/978-3-211-33328-0_2.
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"Pramipexole." In Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions, 2907–8. Elsevier, 2006. http://dx.doi.org/10.1016/b0-44-451005-2/00318-1.
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"Pramipexole." In Meyler's Side Effects of Drugs, 890–91. Elsevier, 2016. http://dx.doi.org/10.1016/b978-0-444-53717-1.01325-1.
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"Pramipexole." In Encyclopedia of Psychopharmacology, 1345–46. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-642-36172-2_201154.
Full textConference papers on the topic "Pramipexolo"
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Paulus, W., U. Friebe-Hoffmann, and W. Janni. "Restless legs in der Schwangerschaft – Pramipexol als therapeutische Option?" In Kongressabstracts zur Tagung 2020 der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG). © 2020. Thieme. All rights reserved., 2020. http://dx.doi.org/10.1055/s-0040-1717170.
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Vasconcelos, Maria Eduarda dos Santos Lopes, José Pedro da Silva Sousa, and Cláudio Eduardo Corrêa Teixeira. "Application of the BlandAltman analysis for quantitative assessment of the degree of agreement between drug prescriptions based or not on bioanthropometric data from neurological patients." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.714.
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Background: The ability to metabolize, absorb, distribute and eliminate drugs is dependent on the genetic profile of each patient, expressed in their functional, metabolic and bioanthropometric phenotypes. Thus, it is relevant to clarify how much these factors impact (or not) the effectiveness of neurological treatment, since its prescription. Design and setting: cross-sectional study (CAAE: 55048816.3.0000.5169). Methods: To assess the degree of agreement between routinely prescribed drug dose values (standard) and drug dose values calculated based on bioanthropometric data (height and mass) of neurological patients, we performed random data collection from 75 patients, both sexes ,>18 yrs, with prescriptions for the use of: carbamazepine, clonazepam, gabapentin, hydantal, rivotril, topiramate, amitriptyline, bupropion, citalopram, duloxetine, donaren, escitalopram, fluoxetine, imipramine, nortriptyline, paroxetine, venabaletine, venabaletine, sertraline, venabaletine, sertraline, venabaletine, serabaletine, pramipexole, prolopa BD, vertix and zolpidem. Data analysis was performed in R. Results: The application of the Bland-Altman analysis revealed that, on average, the prescribed standard drug dose is~10 units higher or lower than the dose calculated based on bioanthropometric data. That is, there is a ~20% disagreement between these different doses. Conclusions: These results should support new investigations on the impact of these differences on the effectiveness of the adopted neurological treatment.
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Pinheiro, Renato Serquiz Elias, Emanuelly da Costa Nobre Soares, Maria Eduarda Bezerra Figueiredo, and Stella Mandu Cicco. "Pisa syndrome in Parkinson’s disease: case description." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.644.
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Context: Pisa Syndrome (PS) is a rare postural disorder, characterized by dystonia of the trunk muscles, lateral deviation as well as rotation of the axial axis. There is a strong association with Parkinson’s disease (PD) due to the possible imbalance between neurotransmitters. It happens either due to a decrease in dopaminergic stimuli, either because of an excess of cholinergic stimuli or drugs (an example of antidopaminergics). The diagnosis is clinical, showing at least a 10-degree trunk flexion with improvement of pharmacological and non- pharmacological measures. Case report: A 60-year-old man was diagnosed with PD five years ago due to tipical clinical complaints and physical examination. The treatment recquired an increase of Pramipexole as well as the use of Levodopa and Benserazide. After two years, he complained about neck pain, low back pain, hip pain and a slight trunk twisting. After six months, his pain was worse and he reported right hemidystonia. Thus, he was diagnosed with PS associated with PD. It was decided to optimize the therapy with Pregabalin, muscle relaxants and rehabilitation. However, it did not show any good result. In 2020, the application of botulinum toxin (BTX) evidenced excellent results, improving both the pain and the spasticity of the patient. Conclusions: Early recognition is necessary to introduce the right treatment as soon as possible, especially BTX and rehabilitation, ensuring functionality and avoiding negative outcomes.
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Marquardt, Matheus, Antônio Serpa do Amaral Neto, Eduardo Martins Leal, Gabriel de Deus Vieira, André Dias de Oliveira, and Gisele Espindola. "Amyotrophic lateral sclerosis associated with parkinsonism: an atypical manifestation." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.608.
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Context: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized by progressive muscle weakness. The diagnosis is not always easy, and may have atypical initial manifestations. Case report: O.S.M, female, 62 years old, started in 2016 with bradykinesia and left lower limb tremor, associated with frequent falls. Iniciated research for parkinsonism in 2017, SPECT demonstrated decreased dopamine transporter binding potential density in both striatum. Levodopa was started, with partial improvement of symptoms. In 2018, she developed dysphagia, associated with slight alterations in phonation. In 2019, in addition to the left lower limb tremor and bradykinesia, the patient developed limb paresis, also affecting the right upper limb, with proximal atrophy and fasciculations. Added to the therapeutic regimen pramipexole, without improvement in symptoms. Over the months the case progressed with axial weakness, the need for a wheelchair for walking. Patient hospitalized in April 2020, electroneuromyography performed which showed signs of active disinvervation in the bulbar, cervical, thoracic and lumbosacral segments and signs of chronic disinervation in the cervical and lumbosacral segments, with no signs of sensory or motor polyneuropathy. Such findings suggest impairment of the Lower motor neuron, and can be found in the Diseases of the Motor Neuron. With the diagnosis of ALS, Riluzole was started, with a reduction in the speed of disease progression. Conclusions: the reported case draws attention to the importance of always thinking about differential diagnoses in neurological diseases. We should always look for new symptoms, so that more rare diseases do not go unnoticed.