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1

Wollman, L. B., K. A. Streeter, and D. D. Fuller. "Ampakine pretreatment enables a single brief hypoxic episode to evoke phrenic motor facilitation." Journal of Neurophysiology 123, no. 3 (2020): 993–1003. http://dx.doi.org/10.1152/jn.00708.2019.

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Phrenic long-term facilitation (LTF) is a sustained increase in phrenic motor output occurring after exposure to multiple (but not single) hypoxic episodes. Ampakines are a class of drugs that enhance AMPA receptor function. Ampakines can enhance expression of neuroplasticity, and the phrenic motor system is fundamentally dependent on excitatory glutamatergic currents. Accordingly, we tested the hypothesis that combining ampakine pretreatment with a single brief hypoxic exposure would result in phrenic motor facilitation lasting well beyond the period of hypoxia. Phrenic nerve output was recor
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2

Turner, S. M., M. K. ElMallah, A. K. Hoyt, J. J. Greer, and D. D. Fuller. "Ampakine CX717 potentiates intermittent hypoxia-induced hypoglossal long-term facilitation." Journal of Neurophysiology 116, no. 3 (2016): 1232–38. http://dx.doi.org/10.1152/jn.00210.2016.

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Glutamatergic currents play a fundamental role in regulating respiratory motor output and are partially mediated by α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors throughout the premotor and motor respiratory circuitry. Ampakines are pharmacological compounds that enhance glutamatergic transmission by altering AMPA receptor channel kinetics. Here, we examined if ampakines alter the expression of respiratory long-term facilitation (LTF), a form of neuroplasticity manifested as a persistent increase in inspiratory activity following brief periods of reduced O2 [intermittent
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3

Su, Chen, Hau Yeuh Lin, Runtao Yang, et al. "AMPAkines Target the Nucleus Accumbens to Relieve Postoperative Pain." Anesthesiology 125, no. 5 (2016): 1030–43. http://dx.doi.org/10.1097/aln.0000000000001336.

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Abstract Background AMPAkines augment the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the brain to increase excitatory outputs. These drugs are known to relieve persistent pain. However, their role in acute pain is unknown. Furthermore, a specific molecular and anatomic target for these novel analgesics remains elusive. Methods The authors studied the analgesic role of an AMPAkine, CX546, in a rat paw incision (PI) model of acute postoperative pain. The authors measured the effect of AMPAkines on sensory and depressive symptoms of pain using mechanical
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4

Ren, Jun, Xiuqing Ding, and John J. Greer. "Respiratory depression in rats induced by alcohol and barbiturate and rescue by ampakine CX717." Journal of Applied Physiology 113, no. 7 (2012): 1004–11. http://dx.doi.org/10.1152/japplphysiol.00752.2012.

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Barbiturate use in conjunction with alcohol can result in severe respiratory depression and overdose deaths. The mechanisms underlying the additive/synergistic actions were unresolved. Current management of ethanol-barbiturate-induced apnea is limited to ventilatory and circulatory support coupled with drug elimination. Based on recent preclinical and clinical studies of opiate-induced respiratory depression, we hypothesized that ampakine compounds may provide a treatment for other types of drug-induced respiratory depression. The actions of alcohol, pentobarbital, bicuculline, and the ampakin
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5

Hachem, LD, AJ Mothe, and CH Tator. "P.089 AMPA receptor modulation as a therapeutic strategy to enhance survival of spinal cord neural stem cells." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 45, s2 (2018): S39—S40. http://dx.doi.org/10.1017/cjn.2018.191.

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Background: Transplantation of neural stem/progenitor cells (NSPCs) following spinal cord injury (SCI) is a promising strategy to enhance regeneration but is limited by poor survival of grafted cells. Recently, we demonstrated for the first time that the excitatory neurotransmitter glutamate, which is released after SCI, promotes survival/proliferation of spinal cord NSPCs via the AMPA subtype of glutamate receptors. Here, we examine the therapeutic potential of selective AMPA receptor modulation on NSPC survival using allosteric AMPA receptor modulators known as ampakines. Methods: NSPCs from
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6

Lin, Vernon W., Christine M. Gall, and Ching-Yi Lin. "Poster 369: Ampakine Treatment Enhances Neurite Outgrowth." PM&R 2 (September 2010): S162—S163. http://dx.doi.org/10.1016/j.pmrj.2010.07.402.

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7

Greer, John J., and Jun Ren. "Ampakine therapy to counter fentanyl-induced respiratory depression." Respiratory Physiology & Neurobiology 168, no. 1-2 (2009): 153–57. http://dx.doi.org/10.1016/j.resp.2009.02.011.

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8

Radin, Daniel P., Yong-Xin Li, Gary Rogers, Richard Purcell, and Arnold Lippa. "Stargazin differentially modulates ampakine gating kinetics and pharmacology." Biochemical Pharmacology 148 (February 2018): 308–14. http://dx.doi.org/10.1016/j.bcp.2018.01.019.

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9

Ingvar, Martin, Jose Ambros-Ingerson, Mike Davis, et al. "Enhancement by an Ampakine of Memory Encoding in Humans." Experimental Neurology 146, no. 2 (1997): 553–59. http://dx.doi.org/10.1006/exnr.1997.6581.

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10

Davis-Reyes, Brionna D., Ashley E. Smith, Jimin Xu, Kathryn A. Cunningham, Jia Zhou, and Noelle C. Anastasio. "Subanesthetic ketamine with an AMPAkine attenuates motor impulsivity in rats." Behavioural Pharmacology 32, no. 4 (2021): 335–44. http://dx.doi.org/10.1097/fbp.0000000000000623.

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11

Arai, A., and M. Kessler. "Pharmacology of Ampakine Modulators: From AMPA Receptors to Synapses and Behavior." Current Drug Targets 8, no. 5 (2007): 583–602. http://dx.doi.org/10.2174/138945007780618490.

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12

Radin, Daniel P., Sheng Zhong, Richard Purcell, and Arnold Lippa. "Acute ampakine treatment ameliorates age-related deficits in long-term potentiation." Biomedicine & Pharmacotherapy 84 (December 2016): 806–9. http://dx.doi.org/10.1016/j.biopha.2016.10.016.

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13

Dai, Wei, Dian Xiao, Xiang Gao, et al. "A brain-targeted ampakine compound protects against opioid-induced respiratory depression." European Journal of Pharmacology 809 (August 2017): 122–29. http://dx.doi.org/10.1016/j.ejphar.2017.05.025.

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14

Ren, Jun, Floriane Lenal, Michael Yang, Xiuqing Ding, and John J. Greer. "Coadministration of the AMPAKINE CX717 with Propofol Reduces Respiratory Depression and Fatal Apneas." Anesthesiology 118, no. 6 (2013): 1437–45. http://dx.doi.org/10.1097/aln.0b013e318291079c.

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Abstract Background: Propofol (2,6-diisopropylphenol) is used for the induction and maintenance of anesthesia in human and veterinary medicine. Propofol’s disadvantages include the induction of respiratory depression and apnea. Here, the authors report a clinically feasible pharmacological solution for reducing propofol-induced respiratory depression via a mechanism that does not interfere with anesthesia. Specifically, they test the hypothesis that the AMPAKINE CX717, which has been proven metabolically stable and safe for human use, can prevent and rescue from propofol-induced severe apnea.
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15

Wesensten, Nancy J., Rebecca M. Reichardt, and Thomas J. Balkin. "Ampakine (CX717) Effects on Performance and Alertness During Simulated Night Shift Work." Aviation, Space, and Environmental Medicine 78, no. 10 (2007): 937–43. http://dx.doi.org/10.3357/asem.2055.2007.

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16

Samartgis, Jodi R., Leslie Schachte, Agnes Hazi, and Simon F. Crowe. "Piracetam, an AMPAkine drug, facilitates memory consolidation in the day-old chick." Pharmacology Biochemistry and Behavior 103, no. 2 (2012): 353–58. http://dx.doi.org/10.1016/j.pbb.2012.08.014.

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17

Silverman, J. L., C. F. Oliver, M. N. Karras, P. T. Gastrell, and J. N. Crawley. "AMPAKINE enhancement of social interaction in the BTBR mouse model of autism." Neuropharmacology 64 (January 2013): 268–82. http://dx.doi.org/10.1016/j.neuropharm.2012.07.013.

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18

Thakre, Prajwal P., Raphael R. Perim, Michael D. Sunshine, Arash Tadjalli, Gordon S. Mitchell, and David D. Fuller. "Spinal delivery of ampakine CX717 impacts phrenic motor output in adult rats." FASEB Journal 34, S1 (2020): 1. http://dx.doi.org/10.1096/fasebj.2020.34.s1.04037.

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19

Lauterborn, Julie C., Linda C. Palmer, Yousheng Jia, et al. "Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged Rats." Journal of Neuroscience 36, no. 5 (2016): 1636–46. http://dx.doi.org/10.1523/jneurosci.3157-15.2016.

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20

Ren, Jun, Xiuqing Ding, Gregory D. Funk, and John J. Greer. "Ampakine CX717 Protects against Fentanyl-induced Respiratory Depression and Lethal Apnea in Rats." Anesthesiology 110, no. 6 (2009): 1364–70. http://dx.doi.org/10.1097/aln.0b013e31819faa2a.

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Background The use of fentanyl as a potent analgesic is contradicted by marked respiratory depression among a subpopulation of patients. The commonly used approach of reversing fentanyl-induced respiratory depression with mu-opiate receptor antagonists such as naloxone has the undesirable effect of blocking analgesia. Here, the authors report a clinically feasible pharmacological solution for countering fentanyl-induced respiratory depression via a mechanism that does not interfere with analgesia. Specifically, to determine if the ampakine CX717, which has been proven metabolically stable and
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21

Xiao, Dian, Fei Xie, Xin Xu, and Xinbo Zhou. "The impact and mechanism of ampakine CX1739 on protection against respiratory depression in rats." Future Medicinal Chemistry 12, no. 23 (2020): 2093–104. http://dx.doi.org/10.4155/fmc-2020-0256.

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Background: Abuse of analgesic and sedative drugs often leads to severe respiratory depression and sometimes death. Approximately 69,000 people worldwide die annually from opioid overdoses. Purpose: This work aimed to investigate whether CX1739 can be used for emergency treatment of acute respiratory depression due to drug abuse. Results: First, the results clarify that CX1739 is a low-impact ampakine that can safely activate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors without causing excito-neurotoxicity. Second, CX1739 rapidly crossed the blood–brain barrier (Tmax =
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22

Zheng, Yiwen, Sangeeta Balabhadrapatruni, Chisako Masumura, Cynthia L. Darlington, and Paul F. Smith. "Effects of the Putative Cognitive-Enhancing Ampakine, CX717, on Attention and Object Recognition Memory." Current Alzheimer Research 8, no. 8 (2011): 876–82. http://dx.doi.org/10.2174/156720511798192709.

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23

Simmons, Danielle A., Rishi A. Mehta, Julie C. Lauterborn, Christine M. Gall, and Gary Lynch. "Brief ampakine treatments slow the progression of Huntington's disease phenotypes in R6/2 mice." Neurobiology of Disease 41, no. 2 (2011): 436–44. http://dx.doi.org/10.1016/j.nbd.2010.10.015.

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24

Goff, Donald C., Leslie Leahy, Ileana Berman, et al. "A Placebo-Controlled Pilot Study of the Ampakine CX516 Added to Clozapine in Schizophrenia." Journal of Clinical Psychopharmacology 21, no. 5 (2001): 484–87. http://dx.doi.org/10.1097/00004714-200110000-00005.

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25

Schitine, Clarissa, Sara Xapelli, Fabienne Agasse, et al. "Ampakine CX546 increases proliferation and neuronal differentiation in subventricular zone stem/progenitor cell cultures." European Journal of Neuroscience 35, no. 11 (2012): 1672–83. http://dx.doi.org/10.1111/j.1460-9568.2012.08072.x.

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26

Lorier, Amanda R., Gregory D. Funk, and John J. Greer. "Opiate-Induced Suppression of Rat Hypoglossal Motoneuron Activity and Its Reversal by Ampakine Therapy." PLoS ONE 5, no. 1 (2010): e8766. http://dx.doi.org/10.1371/journal.pone.0008766.

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27

Radin, Daniel P., Steven Johnson, Richard Purcell, and Arnold S. Lippa. "Effects of chronic systemic low-impact ampakine treatment on neurotrophin expression in rat brain." Biomedicine & Pharmacotherapy 105 (September 2018): 540–44. http://dx.doi.org/10.1016/j.biopha.2018.06.008.

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28

Xiao, Dian, Fan-Hua Meng, Wei Dai, et al. "Design, Synthesis and Biological Evaluation of Brain-Targeted Thiamine Disulfide Prodrugs of Ampakine Compound LCX001." Molecules 21, no. 4 (2016): 488. http://dx.doi.org/10.3390/molecules21040488.

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29

Lipina, Tatiana, Karin Weiss, and John Roder. "The Ampakine CX546 Restores the Prepulse Inhibition and Latent Inhibition Deficits in mGluR5-Deficient Mice." Neuropsychopharmacology 32, no. 4 (2006): 745–56. http://dx.doi.org/10.1038/sj.npp.1301191.

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30

Wezenberg, Elke, Robert Jan Verkes, Ge S. F. Ruigt, Wouter Hulstijn, and Bernard G. C. Sabbe. "Acute Effects of the Ampakine Farampator on Memory and Information Processing in Healthy Elderly Volunteers." Neuropsychopharmacology 32, no. 6 (2006): 1272–83. http://dx.doi.org/10.1038/sj.npp.1301257.

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31

Goff, Donald C., J. Steven Lamberti, Andrew C. Leon, et al. "A Placebo-Controlled Add-On Trial of the Ampakine, CX516, for Cognitive Deficits in Schizophrenia." Neuropsychopharmacology 33, no. 3 (2007): 465–72. http://dx.doi.org/10.1038/sj.npp.1301444.

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32

Gordillo-Salas, M., J. Ren, J. J. Greer, and A. Adell. "The ampakine CX717 has a rapid, but short-lasting antidepressant-like activity in the rat." European Neuropsychopharmacology 29 (2019): S236—S237. http://dx.doi.org/10.1016/j.euroneuro.2018.11.380.

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33

Clarkson, Andrew N., Kim Parker, Michael Nilsson, F. Rohan Walker, and Emma K. Gowing. "Combined Ampakine and BDNF Treatments Enhance Poststroke Functional Recovery in Aged Mice via AKT-CREB Signaling." Journal of Cerebral Blood Flow & Metabolism 35, no. 8 (2015): 1272–79. http://dx.doi.org/10.1038/jcbfm.2015.33.

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Cerebral ischemia results in damage to neuronal circuits and lasting impairment in function. We have previously reported that stimulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors with the ampakine, CX1837, increases brain-derived neurotrophic factor (BDNF) levels and affords significant motor recovery after stroke in young mice. Here, we investigated whether administration of CX1837 in aged (24 months old) mice was equally effective. In a model of focal ischemia, administration of CX1837 from 5 days after stroke resulted in a small gain of motor function by week 6 afte
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34

Simmons, D. A., C. S. Rex, L. Palmer, et al. "Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in Huntington's disease knockin mice." Proceedings of the National Academy of Sciences 106, no. 12 (2009): 4906–11. http://dx.doi.org/10.1073/pnas.0811228106.

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35

Hampson, R. E., R. A. España, G. A. Rogers, L. J. Porrino, and S. A. Deadwyler. "Mechanisms underlying cognitive enhancement and reversal of cognitive deficits in nonhuman primates by the ampakine CX717." Psychopharmacology 202, no. 1-3 (2008): 355–69. http://dx.doi.org/10.1007/s00213-008-1360-z.

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36

Kanju, Patrick M., Kodeeswaran Parameshwaran, Catrina Sims, Ben A. Bahr, Brian C. Shonesy, and Vishnu Suppiramaniam. "Ampakine CX516 ameliorates functional deficits in AMPA receptors in a hippocampal slice model of protein accumulation." Experimental Neurology 214, no. 1 (2008): 55–61. http://dx.doi.org/10.1016/j.expneurol.2008.07.010.

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37

Kariharan, Thiruchelvam, Brian C. Shonesy, Koodeswaran Parameshwaran, and Vishnu D. Suppiramaniam. "P2-440: A memory enhancing drug ampakine (CX-717) potentially modulates synaptic AMPA receptor channel properties." Alzheimer's & Dementia 4 (July 2008): T502. http://dx.doi.org/10.1016/j.jalz.2008.05.1519.

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38

Hampson, Robert E., Gary Rogers, Gary Lynch, and Sam A. Deadwyler. "Facilitative Effects of the Ampakine CX516 on Short-Term Memory in Rats: Correlations with Hippocampal Neuronal Activity." Journal of Neuroscience 18, no. 7 (1998): 2748–63. http://dx.doi.org/10.1523/jneurosci.18-07-02748.1998.

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39

Rana, Sabhya, Michael D. Sunshine, and David D. Fuller. "Impact of Ampakine CX‐717 on Diaphragm EMG Activity and Breathing in Non‐anesthetized Freely Behaving Rats." FASEB Journal 34, S1 (2020): 1. http://dx.doi.org/10.1096/fasebj.2020.34.s1.09742.

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40

Hardouin, Christophe, Frédéric Pin, Jean-François Giffard, et al. "Large Scale Synthesis of an Ampakine-type Active Pharmaceutical Ingredient Based on a Telescoped Regioselective Double Amidation Reaction." Organic Process Research & Development 23, no. 9 (2019): 1932–47. http://dx.doi.org/10.1021/acs.oprd.9b00241.

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41

Marenco, Stefano, Michael F. Egan, Terry E. Goldberg, et al. "Preliminary experience with an ampakine (CX516) as a single agent for the treatment of schizophrenia: a case series." Schizophrenia Research 57, no. 2-3 (2002): 221–26. http://dx.doi.org/10.1016/s0920-9964(01)00311-5.

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42

Boyle, Julia, Neil Stanley, Lynette M. James, et al. "Acute sleep deprivation: the effects of the AMPAKINE compound CX717 on human cognitive performance, alertness and recovery sleep." Journal of Psychopharmacology 26, no. 8 (2011): 1047–57. http://dx.doi.org/10.1177/0269881111405353.

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43

Oertel, B. G., L. Felden, P. V. Tran, et al. "Selective Antagonism of Opioid-Induced Ventilatory Depression by an Ampakine Molecule in Humans Without Loss of Opioid Analgesia." Clinical Pharmacology & Therapeutics 87, no. 2 (2009): 204–11. http://dx.doi.org/10.1038/clpt.2009.194.

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44

Arai, Amy C., Markus Kessler, Gary Rogers, and Gary Lynch. "Effects of the Potent Ampakine CX614 on Hippocampal and Recombinant AMPA Receptors: Interactions with Cyclothiazide and GYKI 52466." Molecular Pharmacology 58, no. 4 (2000): 802–13. http://dx.doi.org/10.1124/mol.58.4.802.

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45

Suppiramaniam, Vishnu, Ben A. Bahr, Srikumar Sinnarajah, et al. "Member of the Ampakine class of memory enhancers prolongs the single channel open time of reconstituted AMPA receptors." Synapse 40, no. 2 (2001): 154–58. http://dx.doi.org/10.1002/syn.1037.

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46

Palmer, Linda C., Ursula S. Hess, John Larson, Gary A. Rogers, Christine M. Gall, and Gary Lynch. "Comparison of the effects of an ampakine with those of methamphetamine on aggregate neuronal activity in cortex versus striatum." Molecular Brain Research 46, no. 1-2 (1997): 127–35. http://dx.doi.org/10.1016/s0169-328x(96)00280-x.

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47

Hampson, Robert E., Gary Rogers, Gary Lynch, and Sam A. Deadwyler. "Facilitative Effects of the Ampakine CX516 on Short-Term Memory in Rats: Enhancement of Delayed-Nonmatch-to-Sample Performance." Journal of Neuroscience 18, no. 7 (1998): 2740–47. http://dx.doi.org/10.1523/jneurosci.18-07-02740.1998.

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48

Haw, Anna J., Leith CR Meyer, John J. Greer, and Andrea Fuller. "Ampakine CX1942 attenuates opioid-induced respiratory depression and corrects the hypoxaemic effects of etorphine in immobilized goats ( Capra hircus )." Veterinary Anaesthesia and Analgesia 43, no. 5 (2016): 528–38. http://dx.doi.org/10.1111/vaa.12358.

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49

Pellerin, Luc, and Pierre J. Magistretti. "Ampakine CX546 bolsters energetic response of astrocytes: A novel target for cognitive-enhancing drugs acting as AMPA receptor modulators." Journal of Cerebral Blood Flow & Metabolism 25, no. 1_suppl (2005): S70. http://dx.doi.org/10.1038/sj.jcbfm.9591524.0070.

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50

Chang, Philip K. Y., George A. Prenosil, David Verbich, Raminder Gill, and R. Anne McKinney. "Prolonged ampakine exposure prunes dendritic spines and increases presynaptic release probability for enhanced long-term potentiation in the hippocampus." European Journal of Neuroscience 40, no. 5 (2014): 2766–76. http://dx.doi.org/10.1111/ejn.12638.

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