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Zacopride









Zacopride


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Zacopride
Zacopride.svg
Clinical data
ATC code
  • none
Identifiers
CAS Number

  • 90182-92-6 ☑Y

PubChem CID
  • 108182
IUPHAR/BPS
  • 245
ChemSpider

  • 97262 ☒N
UNII
  • 9GN3OT4156
ChEMBL

  • ChEMBL18041 ☒N
Chemical and physical data
Formula
C15H20ClN3O2
Molar mass 309.791 g/mol
3D model (JSmol)
  • Interactive image

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 ☒N☑Y (what is this?)
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Zacoprideis a potent antagonist at the 5-HT3 receptor[1] and an agonist at the 5-HT4 receptor.[2] It has anxiolytic[3] and nootropic effects in animal models,[4] with the (R)-(+)-enantiomer being the more active form.[5] It also has antiemetic[6] and pro-respiratory effects, both reducing sleep apnea[7] and reversing opioid-induced respiratory depression in animal studies.[8] Early animal trials have also revealed that administration of zacopride can reduce preference for and consumption of ethanol.[9]


Zacopride was found to significantly increase aldosterone levels in human subjects for 180 minutes at a dose of 400 micrograms. It is thought to do this by stimulating the 5-HT4 receptors on the adrenal glands. Zacopride also stimulated aldosterone secretion when applied to human adrenal glands in vitro. No significant changes were observed in renin, ACTH, or cortisol levels.[2]


Zacopride has been tested in clinical trials for the treatment of schizophrenia, but was found unsuccessful.[10]



References[edit]





  1. ^ Smith, WW; Sancilio, LF; Owera-Atepo, JB; Naylor, RJ; Lambert, L (1988). "Zacopride, a potent 5-HT3 antagonist". The Journal of Pharmacy and Pharmacology. 40 (4): 301–2. doi:10.1111/j.2042-7158.1988.tb05253.x. PMID 2900319..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"""""""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}


  2. ^ ab Lefebvre, H; Contesse, V; Delarue, C; Soubrane, C; Legrand, A; Kuhn, JM; Wolf, LM; Vaudry, H (1993). "Effect of the serotonin-4 receptor agonist zacopride on aldosterone secretion from the human adrenal cortex: in vivo and in vitro studies". The Journal of Clinical Endocrinology and Metabolism. 77 (6): 1662–6. doi:10.1210/jc.77.6.1662. PMID 8263156.


  3. ^ Costall, B; Domeney, AM; Gerrard, PA; Kelly, ME; Naylor, RJ (1988). "Zacopride: anxiolytic profile in rodent and primate models of anxiety". The Journal of Pharmacy and Pharmacology. 40 (4): 302–5. doi:10.1111/j.2042-7158.1988.tb05254.x. PMID 2900320.


  4. ^ Fontana, DJ; Daniels, SE; Eglen, RM; Wong, EH (1996). "Stereoselective effects of (R)- and (S)-zacopride on cognitive performance in a spatial navigation task in rats". Neuropharmacology. 35 (3): 321–7. doi:10.1016/0028-3908(96)00191-8. PMID 8783207.


  5. ^ Young, R; Johnson, DN (1991). "Anxiolytic-like activity of R(+)- and S(−)-zacopride in mice". European Journal of Pharmacology. 201 (2–3): 151–5. doi:10.1016/0014-2999(91)90338-Q. PMID 1686755.


  6. ^ Yamakuni, H; Nakayama, H; Matsui, S; Imazumi, K; Matsuo, M; Mutoh, S (2006). "Inhibitory effect of zacopride on Cisplatin-induced delayed emesis in ferrets". Journal of pharmacological sciences. 101 (1): 99–102. doi:10.1254/jphs.SCJ05007X. PMID 16651699.


  7. ^ Carley, DW; Depoortere, H; Radulovacki, M (2001). "R-zacopride, a 5-HT3 antagonist/5-HT4 agonist, reduces sleep apneas in rats". Pharmacology Biochemistry and Behavior. 69 (1–2): 283–9. doi:10.1016/S0091-3057(01)00535-4. PMID 11420096.


  8. ^ Meyer, LC; Fuller, A; Mitchell, D (2006). "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 (2): R405–13. doi:10.1152/ajpregu.00440.2005. PMID 16166206.


  9. ^ Knapp, D.J.; Pohorecky, L.A. (1992). "Zacopride, a 5-HT3 receptor antagonist, reduces voluntary ethanol consumption in rats". Pharmacology Biochemistry and Behavior. 41 (4): 847–850. doi:10.1016/0091-3057(92)90237-A. ISSN 0091-3057.


  10. ^ Faustman, William O. (1992). "Zacopride in Schizophrenia: A Single-blind Serotonin Type 3 Antagonist Trial". Archives of General Psychiatry. 49 (9): 751. doi:10.1001/archpsyc.1992.01820090079013. ISSN 0003-990X.



















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