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1

Lin, Yuanyuan, Junhu Li, Baozhong Zhu, et al. "Zacopride Exerts an Antiarrhythmic Effect by Specifically Stimulating the Cardiac Inward Rectifier Potassium Current in Rabbits: Exploration of a New Antiarrhythmic Strategy." Current Pharmaceutical Design 26, no. 44 (2020): 5746–54. http://dx.doi.org/10.2174/1381612826666200701135508.

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Background: Zacopride, a potent antagonist of 5-HT3 receptors and an agonist of 5-HT4 receptors, is a gastrointestinal prokinetic agent. In a previous study, we discovered that zacopride selectively stimulated the inward rectifier potassium current (IK1) in the rat and that agonizing IK1 prevented or eliminated aconitine-induced arrhythmias in rats. Objective: Our aims were to confirm that the antiarrhythmic effects of zacopride are mediated by selectively enhancing IK1 in rabbits. Methods: The effects of zacopride on the function of the main ion channels were investigated using a whole-cell p
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2

Wade, P. R., G. M. Mawe, T. A. Branchek, and M. D. Gershon. "Use of stereoisomers of zacopride to analyze actions of 5-hydroxytryptamine on enteric neurons." American Journal of Physiology-Gastrointestinal and Liver Physiology 260, no. 1 (1991): G80—G90. http://dx.doi.org/10.1152/ajpgi.1991.260.1.g80.

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Two subtypes of excitatory 5-hydroxytryptamine (5-HT) receptor, 5-HT1P and 5-HT3, are found on type 2-AH neurons of the guinea pig myenteric plexus. The 5-HT1P receptor mediates a slow and the 5-HT3 receptor a fast depolarization of these cells, however, the role of these receptors in the physiology of the gut is unknown. Renzapride (BRL 24924), a substituted benzamide, has previously been found to antagonize responses of myenteric neurons mediated by both 5-HT1P and 5-HT3 receptors. The effects on myenteric type 2-AH neurons of a structurally similar benzamide, zacopride, which unlike renzapr
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3

&NA;. "Zacopride doesn??t meet expectations." Inpharma Weekly &NA;, no. 858 (1992): 12. http://dx.doi.org/10.2165/00128413-199208580-00018.

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4

SMITH, WILLIAM L., REEVIS S. ALPHIN, CARLOTTA B. JACKSON, and LAWRENCE F. SANCILIO. "The Antiemetic Profile of Zacopride." Journal of Pharmacy and Pharmacology 41, no. 2 (1989): 101–5. http://dx.doi.org/10.1111/j.2042-7158.1989.tb06402.x.

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5

Curtis, Michael J. "Activation of IK1 by Zacopride." Journal of Cardiovascular Pharmacology 64, no. 4 (2014): 343–44. http://dx.doi.org/10.1097/fjc.0000000000000140.

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6

Meyer, Leith C. R., Andrea Fuller, and Duncan Mitchell. "Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 290, no. 2 (2006): R405—R413. http://dx.doi.org/10.1152/ajpregu.00440.2005.

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Neurophysiological studies have shown that serotonergic ligands that bind to 5-HT1A, 5-HT7, and 5-HT4 serotonin receptors in brain stem have beneficial effects on respiratory neurons during opioid-induced respiratory depression. The effect of these ligands on respiratory function and pulmonary performance has not been studied. We therefore examined the effects of 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), an agonist of 5-HT1A and 5-HT7 receptors, and zacopride, an agonist of 5-HT4 receptors, to establish whether these ligands would reverse opioid-induced respiratory depression and hy
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7

SMITH, W. W., L. F. SANCILIO, J. B. OWERA-ATEPO, R. J. NAYLOR, and L. LAMBERT. "Zacopride, a potent 5-HT3 antagonist." Journal of Pharmacy and Pharmacology 40, no. 4 (1988): 301–2. http://dx.doi.org/10.1111/j.2042-7158.1988.tb05253.x.

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8

Ge, Jian, Janine M. Barnes, Patrick Towers, and Nicholas M. Barnes. "Distribution of S(−)-zacopride-insensitive []R(+)-zacopride binding sites in the rat brain and peripheral tissues." European Journal of Pharmacology 332, no. 3 (1997): 307–12. http://dx.doi.org/10.1016/s0014-2999(97)01091-1.

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9

Laporte, A. M., T. Koscielniak, M. Ponchant, D. Vergé, M. Hamon, and H. Gozlan. "Quantitative autoradiographic mapping of 5-HT3receptors in the rat CNS using [125I]iodo-zacopride and [3H]zacopride as radioligands." Synapse 10, no. 4 (1992): 271–81. http://dx.doi.org/10.1002/syn.890100402.

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10

Pisters, K. M. W., M. G. Kris, L. B. Tyson, R. A. Clark, and R. J. Gralla. "Dose-Ranging Trial of Zacopride: The Emetic Antiemetic?" JNCI Journal of the National Cancer Institute 84, no. 9 (1992): 717–18. http://dx.doi.org/10.1093/jnci/84.9.717.

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11

Pinkus, Lawrence M., Nathan S. Sarbin, Dana S. Barefoot, and John C. Gordon. "Association of [3H]zacopride with 5-HT3 binding sites." European Journal of Pharmacology 168, no. 3 (1989): 355–62. http://dx.doi.org/10.1016/0014-2999(89)90797-8.

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12

Makale, M. T., and G. L. King. "Surgical and pharmacological dissociation of cardiovascular and emetic responses to intragastric CuSO4." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 263, no. 2 (1992): R284—R291. http://dx.doi.org/10.1152/ajpregu.1992.263.2.r284.

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Under control (intact and laparotomized) conditions, arterial pressure of urethan-anesthetized ferrets rose significantly in response to intragastric copper sulfate (CuSO4; 10 ml of 5 mg/ml). CuSO4 was emetic 75-90% of the time, and a cardiovascular response always immediately preceded and accompanied emetic responses. The cardiovascular response was significantly reduced or abolished by hexamethonium (0.35 mg/kg) pretreatment combined with atropine methyl bromide (1 mg/kg). Addition of the alpha 2-receptor antagonist 2,3-dichloro-alpha-methylbenzylamine HCl (DCMB, 10 mg/kg) and the beta-recep
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13

COSTALL, B., A. M. DOMENEY, P. A. GERRARD, M. E. KELLY, and R. J. NAYLOR. "Zacopride: anxiolytic profile in rodent and primate models of anxiety." Journal of Pharmacy and Pharmacology 40, no. 4 (1988): 302–5. http://dx.doi.org/10.1111/j.2042-7158.1988.tb05254.x.

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14

Young, Richard, and David N. Johnson. "Anxiolytic-like activity of R(+)- and S(−)-zacopride in mice." European Journal of Pharmacology 201, no. 2-3 (1991): 151–55. http://dx.doi.org/10.1016/0014-2999(91)90338-q.

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15

File, Sandra E., and Nick Andrews. "Enhanced anxiolytic effect of zacopride enantiomers in diazepam-withdrawn rats." European Journal of Pharmacology 237, no. 1 (1993): 127–30. http://dx.doi.org/10.1016/0014-2999(93)90101-m.

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16

Yamakuni, Hisashi, Hiroe Nakayama, Shigeo Matsui, Katsunori Imazumi, Masahiko Matsuo, and Seitaro Mutoh. "Inhibitory Effect of Zacopride on Cisplatin-Induced Delayed Emesis in Ferrets." Journal of Pharmacological Sciences 101, no. 1 (2006): 99–102. http://dx.doi.org/10.1254/jphs.scj05007x.

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17

Faustman, William O. "Zacopride in Schizophrenia: A Single-blind Serotonin Type 3 Antagonist Trial." Archives of General Psychiatry 49, no. 9 (1992): 751. http://dx.doi.org/10.1001/archpsyc.1992.01820090079013.

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18

BARNES, N. M., B. COSTALL, and R. J. NAYLOR. "[3H]Zacopride: Ligand for the Identification of 5-HT3 Recognition Sites." Journal of Pharmacy and Pharmacology 40, no. 8 (1988): 548–51. http://dx.doi.org/10.1111/j.2042-7158.1988.tb05300.x.

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19

Eglen, Richard M. "Monthly Update: The (R) zacopride binding site:Central & Peripheral Nervous Systems." Expert Opinion on Investigational Drugs 4, no. 3 (1995): 229–31. http://dx.doi.org/10.1517/13543784.4.3.229.

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20

Ansseau, M., W. Pitchot, and A. Gonzalez Moreno. "Anxiolytic activity of single doses of the 5-HT3 antagonist zacopride." European Neuropsychopharmacology 4, no. 3 (1994): 355. http://dx.doi.org/10.1016/0924-977x(94)90177-5.

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21

Boddeke, Hendrik W. G. M., and Hans O. Kalkman. "Zacopride and BRL 24924 induce an increase in EEG-energy in rats." British Journal of Pharmacology 101, no. 2 (1990): 281–84. http://dx.doi.org/10.1111/j.1476-5381.1990.tb12701.x.

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22

Knapp, D. J., and L. A. Pohorecky. "Zacopride, a 5-HT3 receptor antagonist, reduces voluntary ethanol consumption in rats." Pharmacology Biochemistry and Behavior 41, no. 4 (1992): 847–50. http://dx.doi.org/10.1016/0091-3057(92)90237-a.

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23

Sancilio, Lawrence F., Lawrence M. Pinkus, Carlotta B. Jackson, and H. Randall Munson. "Studies on the emetic and antiemetic properties of zacopride and its enantiomers." European Journal of Pharmacology 192, no. 3 (1991): 365–69. http://dx.doi.org/10.1016/0014-2999(91)90226-g.

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24

Sancilio, Lawrence F., Lawrence M. Pinkus, Carlotta B. Jackson, and H. Randall Munson. "Emetic activity of zacopride in ferrets and its antagonism by pharmacological agents." European Journal of Pharmacology 181, no. 3 (1990): 303–6. http://dx.doi.org/10.1016/0014-2999(90)90094-m.

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25

Richmond, G., S. G. Potkin, L. Plon, T. McElroy, and Y. Jin. "Zacopride, A 5-HT3 receptor antagonist, may be an effective antipsychotic in schizophrenia." Schizophrenia Research 9, no. 2-3 (1993): 247–48. http://dx.doi.org/10.1016/0920-9964(93)90559-2.

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26

BARNES, NICHOLAS M., BRENDA COSTALL, JAMES W. IRONSIDE, and ROBERT L. NAYLOR. "Identification of 5-HT3 recognition sites in human brain tissue using [3H]zacopride." Journal of Pharmacy and Pharmacology 40, no. 9 (1988): 668. http://dx.doi.org/10.1111/j.2042-7158.1988.tb05338.x.

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27

Barnes, J. M., N. M. Barnes, B. Costall, et al. "The differential activities of R(+)- and S(−)-zacopride as 5-HT3 receptor antagonists." Pharmacology Biochemistry and Behavior 37, no. 4 (1990): 717–27. http://dx.doi.org/10.1016/0091-3057(90)90554-u.

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28

Mele, Paul C., John R. McDonough, David B. McLean, and Kevin P. O'Halloran. "Cisplatin-induced conditioned taste aversion: attenuation by dexamethasone but not zacopride or GR38032F." European Journal of Pharmacology 218, no. 2-3 (1992): 229–36. http://dx.doi.org/10.1016/0014-2999(92)90173-2.

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29

Carley, David W., Henri Depoortere, and Miodrag Radulovacki. "R-zacopride, a 5-HT3 antagonist/5-HT4 agonist, reduces sleep apneas in rats." Pharmacology Biochemistry and Behavior 69, no. 1-2 (2001): 283–89. http://dx.doi.org/10.1016/s0091-3057(01)00535-4.

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30

Zhai, Xuwen, Xi Qiao, Li Zhang, et al. "IK1 channel agonist zacopride suppresses ventricular arrhythmias in conscious rats with healing myocardial infarction." Life Sciences 239 (December 2019): 117075. http://dx.doi.org/10.1016/j.lfs.2019.117075.

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31

Fletcher, Stephanie, and Nicholas M. Barnes. "Autoradiographic localization of the [3H]-(S)-zacopride labelled 5-HT3 receptor in porcine brain." Neuroscience Letters 269, no. 2 (1999): 91–94. http://dx.doi.org/10.1016/s0304-3940(99)00429-2.

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32

Smith, William L., Esther M. Callaham, and Reevis S. Alphin. "The emetic activity of centrally administered cisplatin in cats and its antagonism by zacopride." Journal of Pharmacy and Pharmacology 40, no. 2 (1988): 142–43. http://dx.doi.org/10.1111/j.2042-7158.1988.tb05202.x.

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33

Zhang, Li, QingHua Liu, ChengFang Liu, et al. "Zacopride selectively activates the Kir2.1 channel via a PKA signaling pathway in rat cardiomyocytes." Science China Life Sciences 56, no. 9 (2013): 788–96. http://dx.doi.org/10.1007/s11427-013-4531-z.

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34

Young, Richard, and Richard A. Glennon. "Zacopride and its optical isomers produce stereoselective antagonism of a 2-methylserotonin discriminative stimulus." European Journal of Pharmacology 212, no. 1 (1992): 117–19. http://dx.doi.org/10.1016/0014-2999(92)90083-g.

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35

Barnes, Nicholas M., Brenda Costall, Jian Ge, M. Elizabeth Kelly, and Robert J. Naylor. "The interaction of R(+)- and S(-)-zacopride with PCPA to modify rodent aversive behaviour." European Journal of Pharmacology 218, no. 1 (1992): 15–25. http://dx.doi.org/10.1016/0014-2999(92)90142-q.

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36

Barnes, Nicholas M., Celine H. K. Cheng, Brenda Costall, Jian Ge, M. Elizabeth Kelly, and Robert J. Naylor. "Profiles of interaction of R(+)/S(-)-zacopride and anxiolytic agents in a mouse model." European Journal of Pharmacology 218, no. 1 (1992): 91–100. http://dx.doi.org/10.1016/0014-2999(92)90151-s.

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37

Parker, Rachel M. C., Janine M. Barnes, Jian Ge, Peter C. Barber, and Nicholas M. Barnes. "Autoradiographic distribution of [ 3 H]-(S)-zacopride-labelled 5-HT 3 receptors in human brain." Journal of the Neurological Sciences 144, no. 1-2 (1996): 119–27. http://dx.doi.org/10.1016/s0022-510x(96)00211-0.

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38

Wu, Bei, Cun Long, Feilong Hei, and Shilei Wang. "The Protective Effect of St. Thomas Cardioplegia Enriched With Zacopride on the Isolated Rat Heart." Artificial Organs 37, no. 1 (2012): E44—E50. http://dx.doi.org/10.1111/j.1525-1594.2012.01547.x.

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39

Zhai, Xu-Wen, Li Zhang, Yun-Fei Guo, et al. "The IK1/Kir2.1 channel agonist zacopride prevents and cures acute ischemic arrhythmias in the rat." PLOS ONE 12, no. 5 (2017): e0177600. http://dx.doi.org/10.1371/journal.pone.0177600.

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40

Wu, Bo-Wei. "Activation of IK1 Channel by Zacopride Attenuates Left Ventricular Remodeling in Rats With Myocardial Infarction." Journal of Cardiovascular Pharmacology 65, no. 3 (2015): 296. http://dx.doi.org/10.1097/01.fjc.0000462727.05737.2c.

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41

Liu, Cheng-Fang, Qing-Hua Liu, En-Li Liu, et al. "Activation of IK1 Channel by Zacopride Attenuates Left Ventricular Remodeling in Rats With Myocardial Infarction." Journal of Cardiovascular Pharmacology 64, no. 4 (2014): 345–56. http://dx.doi.org/10.1097/fjc.0000000000000127.

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42

Wu, Bo-Wei, and Ji-Min Cao. "On the Risk Concerns of Zacopride, a Moderate IK1 Channel Agonist With Cardiac Protective Action." Journal of Cardiovascular Pharmacology 64, no. 4 (2014): 357–59. http://dx.doi.org/10.1097/fjc.0000000000000148.

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43

Bourdin, Céline M., Jacques Lebreton, Monique Mathé-Allainmat та Steeve H. Thany. "Pharmacological profile of zacopride and new quaternarized fluorobenzamide analogues on mammalian α7 nicotinic acetylcholine receptor". Bioorganic & Medicinal Chemistry Letters 25, № 16 (2015): 3184–88. http://dx.doi.org/10.1016/j.bmcl.2015.05.094.

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44

Fletcher, Stephanie, and Nicholas M. Barnes. "Distribution and characterisation of the [3H](S)-zacopride labelled 5-HT3 receptor in pig forebrain." Brain Research 729, no. 2 (1996): 281–84. http://dx.doi.org/10.1016/0006-8993(96)00589-6.

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45

Ponchant, M., T. Koscielniak, M. Hamon, and H. Gozlan. "Synthesis of 5-[125I]-iodo-zacopride, a new probe for 5-HT3 receptor binding sites." Journal of Labelled Compounds and Radiopharmaceuticals 29, no. 10 (1991): 1147–55. http://dx.doi.org/10.1002/jlcr.2580291007.

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46

Pinkus, Lawrence M., Nathan S. Sarbin, John C. Gordon, and H. Randall Munson. "Antagonism of [3H]zacopride binding to 5-HT3 recognition sites by its (R) and (S) enantiomers." European Journal of Pharmacology 179, no. 1-2 (1990): 231–35. http://dx.doi.org/10.1016/0014-2999(90)90425-6.

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47

Bill, David J., James Coleman, Ian Hallett, Vicki C. Middlefell, Keith F. Rhodes, and Allan Fletcher. "The enantiomers of zacopride: an intra-species comparison of their potencies in functional and anxiolytic models." British Journal of Pharmacology 115, no. 5 (1995): 775–80. http://dx.doi.org/10.1111/j.1476-5381.1995.tb15000.x.

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48

Middlefell, Vicki C., and Tracey L. Price. "5-HT3 receptor agonism may be responsible for the emetic effects of zacopride in the ferret." British Journal of Pharmacology 103, no. 1 (1991): 1011–12. http://dx.doi.org/10.1111/j.1476-5381.1991.tb12292.x.

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49

McNeish, Charles S., Adena L. Svingos, Robert Hitzemann, and Robert E. Strecker. "The 5-HT3 antagonist zacopride attenuates cocaine-induced increases in extracellular dopamine in rat nucleus accumbens." Pharmacology Biochemistry and Behavior 45, no. 4 (1993): 759–63. http://dx.doi.org/10.1016/0091-3057(93)90118-d.

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50

Lefebvre, H., V. Contesse, C. Delarue, J. M. Kuhn, H. Vaudry, and L. M. Wolf. "Lack of effect of the serotonin 4 receptor agonist zacopride on ACTH secretion in normal men." European Journal of Clinical Pharmacology 51, no. 1 (1996): 49–51. http://dx.doi.org/10.1007/s002280050159.

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