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1

Prins, S. A., S. J. A. Pans, M. M. van Weissenbruch, F. J. Walther, and S. H. P. Simons. "Doxapram Use for Apnoea of Prematurity in Neonatal Intensive Care." International Journal of Pediatrics 2013 (2013): 1–5. http://dx.doi.org/10.1155/2013/251047.

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Apnoea of prematurity is treated with noninvasive respiratory therapy and methylxanthines. For therapy unresponsive apnoea doxapram is often prescibed in preterm neonates. The duration, dosage and route of administration of doxapram together with its efficacy was evaluated in two Dutch neonatal intensive care. Outcome concerning short-term safety and neonatal morbidity were evaluated. During 5 years, 122 of 1,501 admitted newborns <32 weeks of gestational age received doxapram. 64.8% of patients did not need intubation after doxapram. 25% of treated neonates were <27 weeks of gestation.
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2

Engbers, Aline G. J., Swantje Völler, Christian F. Poets, et al. "The Pharmacokinetics of Caffeine in Preterm Newborns: No Influence of Doxapram but Important Maturation with Age." Neonatology 118, no. 1 (2021): 106–13. http://dx.doi.org/10.1159/000513413.

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Background: Apnea of prematurity can persist despite caffeine therapy in preterm infants. Doxapram may additionally support breathing. Although multiple small studies have reported the efficacy of doxapram, the structural co-treatment with caffeine impedes to ascribe the efficacy to doxapram itself or to a pharmacokinetic (PK) interaction where doxapram increases the exposure to caffeine. We examined whether there is a PK drug-drug interaction between doxapram and caffeine by developing a PK model for caffeine including infants with and without doxapram treatment. Methods: In preterm neonates
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3

Heggem, Brittany. "Doxapram." Journal of Exotic Pet Medicine 20, no. 3 (2011): 237–40. http://dx.doi.org/10.1053/j.jepm.2011.04.011.

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4

Shrestha, Amir Babu. "Comparative Study on Effectiveness of Doxapram and Pethidine for Postanaesthetic Shivering." Journal of Nepal Medical Association 48, no. 174 (2009): 116–20. http://dx.doi.org/10.31729/jnma.225.

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Introduction: Postanaesthetic shivering is a common condition after surgery which needs proper management with pharmacologic agents so as to make postoperative period comfortable to the patient and prevent from the untoward complications that can arise from it. This study was done to compare the effectiveness of Pethidine and Doxapram in the treatment of postanaesthetic shivering.Methods: Patients were randomly divided into three groups, ten in each. All received volume of 3 ml as Group I (Doxapram 1.5 mg/kg), Group II (Pethidine 0.35 mg/kg) and Group III (Normal Saline). All patients were obs
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5

&NA;. "Cisapride/doxapram." Reactions Weekly &NA;, no. 715 (1998): 6. http://dx.doi.org/10.2165/00128415-199807150-00015.

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6

Cote, A., P. W. Blanchard, and B. Meehan. "Metabolic and cardiorespiratory effects of doxapram and theophylline in sleeping newborn piglets." Journal of Applied Physiology 72, no. 2 (1992): 410–15. http://dx.doi.org/10.1152/jappl.1992.72.2.410.

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To evaluate the contribution of a change in metabolic rate to ventilatory changes after the administration of respiratory stimulants, we studied the effect of two respiratory stimulants, doxapram and theophylline, on ventilation and metabolic rate during sleep in piglets. Metabolic rate (O2 consumption and CO2 production) was measured in a metabolic chamber, and alveolar ventilation (VA) was derived from arterial PCO2 and CO2 production. We studied the animals during a baseline period and for 2 h after the administration of theophylline or doxapram. With doxapram, there was no change in VA, me
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7

Kruszynski, Sandra, Kornelijus Stanaitis, Janine Brandes, Christian F. Poets, and Henner Koch. "Doxapram stimulates respiratory activity through distinct activation of neurons in the nucleus hypoglossus and the pre-Bötzinger complex." Journal of Neurophysiology 121, no. 4 (2019): 1102–10. http://dx.doi.org/10.1152/jn.00304.2018.

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Doxapram is a respiratory stimulant used for decades as a treatment option in apnea of prematurity refractory to methylxanthine treatment. Its mode of action, however, is still poorly understood. We investigated direct effects of doxapram on the pre-Bötzinger complex (PreBötC) and on a downstream motor output system, the hypoglossal nucleus (XII), in the transverse brainstem slice preparation. While doxapram has only a modest stimulatory effect on frequency of activity generated within the PreBötC, a much more robust increase in the amplitude of population activity in the subsequent motor outp
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8

Wilkinson, Katherine A., Kimberly Huey, Bruce Dinger, Liang He, Salvatore Fidone, and Frank L. Powell. "Chronic hypoxia increases the gain of the hypoxic ventilatory response by a mechanism in the central nervous system." Journal of Applied Physiology 109, no. 2 (2010): 424–30. http://dx.doi.org/10.1152/japplphysiol.01311.2009.

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We studied the effects of the ventilatory stimulant doxapram to test the hypothesis that chronic hypoxia increases the translation of carotid body afferent input into ventilatory motor efferent output by the central nervous system. Chronic hypoxia (inspired Po2 = 70 Torr, 2 days) significantly increased the ventilatory response to an intravenous infusion of a high dose of doxapram in conscious, unrestrained rats breathing normoxic or hypoxic gas. The in vitro carotid body response to hypoxia increased with chronic hypoxia, but the response was not increased with a high dose of doxapram. Simila
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9

Engbers, A., N. Dia, S. Völler, et al. "P31 No interaction between doxapram and caffeine for the treatment of preterm neonates with apnea." Archives of Disease in Childhood 104, no. 6 (2019): e29.3-e30. http://dx.doi.org/10.1136/archdischild-2019-esdppp.69.

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BackgroundIn preterm neonates with apneas, co-administration with doxapram is often initiated in case of inadequate response to caffeine alone. While doxapram is exclusively registered for adults, there is limited information on its use in preterm infants. To examine whether the observed effects of doxapram are actually due to doxapram itself, and not a pharmacokinetic interaction between both respiratory stimulants, we studied the pharmacokinetics (PK) of caffeine in a population of preterm neonates receiving both caffeine and doxapram.MethodsCaffeine concentrations from patients in the DINO
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10

Poppe, JA, W. van Weteringen, S. Völler, TG Goos, IKM Reiss, and SHP Simons. "P80 Objective pharmacodynamic evaluation of doxapram in preterm infants." Archives of Disease in Childhood 104, no. 6 (2019): e50.1-e50. http://dx.doi.org/10.1136/archdischild-2019-esdppp.118.

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BackgroundPharmacodynamic evaluation is challenging in neonatal clinical care, and often based on subjective human interpretation of clinical signs and the available ‘snapshot’ of physiological parameters. High frequency data (≥ 1Hz) of bedside patient monitors provide the opportunity of continuous and objective drug evaluation.1 This study investigates the predictive value of continuously available vital and ventilatory parameters to evaluate doxapram therapy. Doxapram is a respiratory stimulant to avoid mechanical ventilation and adverse outcomes of hypoxemia in preterm infants.2MethodsPrete
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11

Oikawa, Shota, Hiroko Nomura, Miki Nishio, Rina Nagata, and Tadayoshi Hata. "Doxapram Hydrochloride Aggravates Adrenaline-Induced Arrhythmias Accompanied by Bidirectional Ventricular Tachycardia." ISRN Cardiology 2014 (January 9, 2014): 1–5. http://dx.doi.org/10.1155/2014/212045.

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Objectives. Doxapram hydrochloride is a respiratory stimulant that has an inhibitory effect on myocardial IK1 potassium channels and is thought to increase membrane instability and excitability in myocardial cells. We examined the arrhythmogenic effects of doxapram hydrochloride in a rat model of halothane adrenaline-induced arrhythmia. Methods. Thirteen female Wistar rats (12–14 weeks old) were used in the study. Animals were anesthetized with inhalation of halothane to permit observation of the effects of doxapram hydrochloride on halothane adrenaline-induced arrhythmia. Time-dependent chang
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12

Gautier, H. "Doxapram and shivering." Anaesthesia 46, no. 12 (1991): 1092–93. http://dx.doi.org/10.1111/j.1365-2044.1991.tb09954.x.

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13

McKeirnan, Kelci L., Marjorie E. Gross, Mark Rochat, and Mark Payton. "Comparison of Propofol and Propofol/Ketamine Anesthesia for Evaluation of Laryngeal Function in Healthy Dogs." Journal of the American Animal Hospital Association 50, no. 1 (2014): 19–26. http://dx.doi.org/10.5326/jaaha-ms-5959.

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Thiopental is an excellent choice for evaluation of laryngeal function. Unfortunately, thiopental is no longer manufactured. In its absence, the ideal anesthetic protocol for laryngoscopy has not been determined. Propofol and propofol/ketamine were compared for the evaluation of laryngeal function in 48 healthy dogs. Laryngeal exposure was moderate to excellent in all dogs and not significantly different between protocols. Saturation of peripheral O2 (SPO2) readings were decreased in the propofol/ketamine group, and deeper respirations were more likely to correlate with normal laryngeal functi
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14

Flint, RB, SHP Simons, P. Andriessen, et al. "O17 The bioavailability and maturing clearance of doxapram in preterm infants." Archives of Disease in Childhood 104, no. 6 (2019): e8.1-e8. http://dx.doi.org/10.1136/archdischild-2019-esdppp.17.

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BackgroundDoxapram is used for intravenous and oral treatment of apnea of prematurity in preterm infants. Dosing is currently based on bodyweight, however pharmacokinetic and bioavailability data are limited. To develop individualized dosing strategies, we characterized pharmacokinetics of doxapram in this vulnerable patient population.MethodsData (302 samples) from 75 neonates were included with median (range) gestational age (GA) 25.9 (23.9–29.4) weeks, bodyweight 0.95 (0.48–1.61) kg, postnatal age (PNA) 17 (1–52) days at start of continuous treatment, and treatment duration of 16.8 (1.4–26.
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15

McGuire, Michelle, Michael F. Carey, and John J. O’Connor. "Almitrine and doxapram decrease fatigue and increase subsequent recovery in isolated rat diaphragm." Journal of Applied Physiology 83, no. 1 (1997): 52–58. http://dx.doi.org/10.1152/jappl.1997.83.1.52.

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McGuire, Michelle, Michael F. Carey, and John J. O’Connor.Almitrine and doxapram decrease fatigue and increase subsequent recovery in isolated rat diaphragm. J. Appl. Physiol. 83(1): 52–58, 1997.—The effects of almitrine bimesylate and doxapram HCl on isometric force produced by in vitro rat diaphragm were studied during direct muscle activation at 37°C. Doxapram and almitrine ameliorate respiratory failure clinically by indirectly increasing phrenic nerve activity. This study was carried out to investigate possible direct actions of these agents on the diaphragm before and after fatigue of th
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16

SARMA, V., and N. S. FRY. "Doxapram After General Anesthesia." Survey of Anesthesiology 36, no. 2 (1992): 66. http://dx.doi.org/10.1097/00132586-199204000-00015.

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17

Broome, I. J., and G. H. Mills. "Doxapram after general anaesthesia." Anaesthesia 47, no. 4 (1992): 363. http://dx.doi.org/10.1111/j.1365-2044.1992.tb02206.x.

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18

Sarma, V. "Doxapram after general anaesthesia." Anaesthesia 47, no. 4 (1992): 364. http://dx.doi.org/10.1111/j.1365-2044.1992.tb02207.x.

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19

Finer, Neil N., and Keith J. Barrington. "Doxapram and neurodevelopmental outcome." Journal of Pediatrics 141, no. 2 (2002): 0296. http://dx.doi.org/10.1067/mpd.2002.126008.

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20

&NA;. "Doxapram stops postoperative shivering." Inpharma Weekly &NA;, no. 794 (1991): 10. http://dx.doi.org/10.2165/00128413-199107940-00027.

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21

SARMA, V., and E. N. S. FRY. "Doxapram after general anaesthesia." Anaesthesia 46, no. 6 (1991): 460–61. http://dx.doi.org/10.1111/j.1365-2044.1991.tb11683.x.

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22

Poppe, Jarinda A., Willem van Weteringen, Swantje Völler, et al. "Use of Continuous Physiological Monitor Data to Evaluate Doxapram Therapy in Preterm Infants." Neonatology 117, no. 4 (2020): 438–45. http://dx.doi.org/10.1159/000509269.

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<b><i>Introduction:</i></b> Evaluation of pharmacotherapy during intensive care treatment is commonly based on subjective, intermittent interpretations of physiological parameters. Real-time visualization and analysis may improve drug effect evaluation. We aimed to evaluate the effects of the respiratory stimulant doxapram objectively in preterm infants using continuous physiological parameters. <b><i>Methods:</i></b> In this longitudinal observational study, preterm infants who received doxapram therapy were eligible for inclusion. Physiological
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23

Bairam, A., P. W. Blanchard, K. Mullahoo, K. Beharry, N. Laudignon, and J. V. Aranda. "Pharmacodynamic Effects and Pharmacokinetic Profiles of Keto-Doxapram and Doxapram in Newborn Lambs." Pediatric Research 28, no. 2 (1990): 142–46. http://dx.doi.org/10.1203/00006450-199008000-00013.

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24

BAIRAM, A., P. W. BLANCHARD, K. MULLAHOO, K. BEHARRY, N. LAUDIGNON, and J. V. ARANDA. "Pharmacodynamic Effects and Pharmacokinetic Profiles of Keto-Doxapram and Doxapram in Newborn Lambs1." Pediatric Research 28, no. 2 (1990): 142–46. http://dx.doi.org/10.1203/00006450-199028020-00013.

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25

Cater, Gary, Stan Shaffer, and Robert T. Hall. "Doxapram for apnea of prematurity." Journal of Pediatrics 109, no. 3 (1986): 563. http://dx.doi.org/10.1016/s0022-3476(86)80146-9.

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26

POLLARD, B. J., N. P. C. RANDALL, and B. J. PLEUVRY. "DOXAPRAM AND THE NEUROMUSCULAR JUNCTION †." British Journal of Anaesthesia 62, no. 6 (1989): 664–68. http://dx.doi.org/10.1093/bja/62.6.664.

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27

FAUVEL, N. J., and S. A. FELDMAN. "DOXAPRAM AND THE NEUROMUSCULAR JUNCTION." British Journal of Anaesthesia 64, no. 2 (1990): 256. http://dx.doi.org/10.1093/bja/64.2.256-b.

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28

Ebihara, Satoru, Hiromasa Ogawa, Hidetada Sasaki, Wataru Hida, and Yoshihiro Kikuchi. "Doxapram and Perception of Dyspnea." Chest 121, no. 4 (2002): 1380–81. http://dx.doi.org/10.1378/chest.121.4.1380.

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29

Rose, Stephen J., David J. Lloyd, and Paul Duffty. "Doxapram for apnea of prematurity." Journal of Pediatrics 111, no. 1 (1987): 154. http://dx.doi.org/10.1016/s0022-3476(87)80368-2.

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30

&NA;. "Doxapram reduces postoperative pulmonary complications." Inpharma Weekly &NA;, no. 735 (1990): 12. http://dx.doi.org/10.2165/00128413-199007350-00026.

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31

Fancourt, G. J., R. J. Ashton, I. C. Talbot, and J. M. Wales. "Hepatic necrosis with doxapram hydrochloride." Postgraduate Medical Journal 61, no. 719 (1985): 833–35. http://dx.doi.org/10.1136/pgmj.61.719.833.

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32

Krasikovs, Andrejs. "Enantioselective formal synthesis of doxapram." Chemistry of Heterocyclic Compounds 51, no. 4 (2015): 385–88. http://dx.doi.org/10.1007/s10593-015-1712-7.

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33

Lee, Yue-Joe, George C. Curtis, John G. Weg, James L. Abelson, Jack G. Modell, and Kelly M. Campbell. "Panic attacks induced by doxapram." Biological Psychiatry 33, no. 4 (1993): 295–97. http://dx.doi.org/10.1016/0006-3223(93)90299-s.

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34

&NA;. "Doxapram affects mental development in infants?" Inpharma Weekly &NA;, no. 1324 (2002): 21. http://dx.doi.org/10.2165/00128413-200213240-00051.

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35

&NA;. "Doxapram affects mental development in infants?" Reactions Weekly &NA;, no. 888 (2002): 5. http://dx.doi.org/10.2165/00128415-200208880-00010.

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36

&NA;. "Doxapram hastens recovery from sevoflurane anaesthesia,." Inpharma Weekly &NA;, no. 1543 (2006): 18. http://dx.doi.org/10.2165/00128413-200615430-00049.

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37

Bairam, Aida, Lynne Akramoff-Gershan, Kae Beharry, Nicole Laudignon, Apostolos Papageorgiou, and Jacob Aranda. "Gastrointestinal Absorption of Doxapram in Neonates." American Journal of Perinatology 8, no. 02 (1991): 110–13. http://dx.doi.org/10.1055/s-2007-999357.

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38

Aranda, J. V., A. Mendelberg, K. Beharry, J. Rex, Q. Pelea, and F. Eval. "METABOLISM OF DOXAPRAM IN PREMATURE NEWBORNS." Pediatric Research 21, no. 4 (1987): 232A. http://dx.doi.org/10.1203/00006450-198704010-00394.

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39

&NA;. "Theophylline and doxapram have comparable efficacy." Inpharma Weekly &NA;, no. 735 (1990): 14–15. http://dx.doi.org/10.2165/00128413-199007350-00035.

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40

Li, Eric, Ganan Sritharan, Mariana Mogos, Peter Roffey, and Duraiyah Thangathurai. "Doxapram Revisited in Patients with Cancer." Journal of Palliative Medicine 12, no. 8 (2009): 673. http://dx.doi.org/10.1089/jpm.2009.0073.

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41

Wu, Chi-Chen, Martin S. Mok, Jui-Yuan Chen, Gong-Jhe Wu, Yeong-Ray Wen, and Chao-Shun Lin. "Doxapram shortens recovery following sevoflurane anesthesia." Canadian Journal of Anesthesia/Journal canadien d'anesthésie 53, no. 5 (2006): 456–60. http://dx.doi.org/10.1007/bf03022617.

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42

Gutman, David A., Jeremy Coplan, Laszlo Papp, Jose Martinez, and Jack Gorman. "Doxapram-induced panic attacks and cortisol elevation." Psychiatry Research 133, no. 2-3 (2005): 253–61. http://dx.doi.org/10.1016/j.psychres.2004.10.010.

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43

Bairam, A., and P. Vert. "LOW-DOSE DOXAPRAM FOR APNOEA OF PREMATURITY." Lancet 327, no. 8484 (1986): 793–94. http://dx.doi.org/10.1016/s0140-6736(86)91796-4.

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44

Ishikawa, Masaaki, Ichiko Suzuki, Masayasu Ozaki, Yoshio Takayanagi, and Ken-ichi Sasaki. "Interaction of Doxapram and Pentobarbital in Mice." Pharmacology & Toxicology 69, no. 4 (1991): 276–81. http://dx.doi.org/10.1111/bcpt.1991.69.4.276.

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45

Leeman, Marc, Marion Delcroix, Jean-Luc Vachiéry, Christian Mélot, and Robert Naeije. "Almitrine and Doxapram in Experimental Lung Injury." American Review of Respiratory Disease 145, no. 5 (1992): 1042–46. http://dx.doi.org/10.1164/ajrccm/145.5.1042.

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46

TAYLOR, POLLY M. "Doxapram infusion during halothane anaesthesia in ponies." Equine Veterinary Journal 22, no. 5 (1990): 329–32. http://dx.doi.org/10.1111/j.2042-3306.1990.tb04284.x.

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47

Coutts, R. T., F. Jamali, F. Malek, A. Peliowski, and N. N. Finer. "Urinary metabolites of doxapram in premature neonates." Xenobiotica 21, no. 10 (1991): 1407–18. http://dx.doi.org/10.3109/00498259109043215.

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48

ThangaThurai, D., D. Nelson, and M. Cheung. "Doxapram for respiratory depression after epidural morphine." Anaesthesia 45, no. 1 (1990): 64–65. http://dx.doi.org/10.1111/j.1365-2044.1990.tb14524.x.

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49

Osanai, S., T. Takahashi, H. Nakano, and K. Kikuchi. "Doxapram inhibits carotid sinus baroreceptors in rabbits." Autonomic and Autacoid Pharmacology 25, no. 2 (2005): 79–84. http://dx.doi.org/10.1111/j.1474-8673.2005.00336.x.

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50

Sandhu, M. S., K. Z. Lee, E. J. Gonzalez-Rothi, and D. D. Fuller. "Repeated intravenous doxapram induces phrenic motor facilitation." Experimental Neurology 250 (December 2013): 108–15. http://dx.doi.org/10.1016/j.expneurol.2013.08.016.

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