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Zacopride

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Zacopride
Clinical data
ATC code
  • none
Identifiers
  • 4-amino-5-chloro-2-methoxy-N-(quinuclidin-3-yl)benzamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC15H20ClN3O2
Molar mass309.791 g/mol g·mol−1
3D model (JSmol)
  • COC1=CC(=C(C=C1C(=O)NC2CN3CCC2CC3)Cl)N
  • InChI=1S/C15H20ClN3O2/c1-21-14-7-12(17)11(16)6-10(14)15(20)18-13-8-19-4-2-9(13)3-5-19/h6-7,9,13H,2-5,8,17H2,1H3,(H,18,20) ☒N
  • Key:FEROPKNOYKURCJ-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Zacopride is 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 apnoea[7] and reversing opioid-induced respiratory depression in animal studies.[8]

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. Zacropride also stimulated aldosterone secretion when applied to human adrenal glands in vitro. No significant changes were observed in renin, ACTH, or cortisol levels.[2]

Synthesis

Zacopride synthesis:[9]

Reaction with 3-aminoquinuclidine[10][11][12] of the intermediate prepared from acid 4 with carbonyldiimidazole (CDI) affords zaclopride (5).

See also

References

  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.
  2. ^ a b 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. ^ L. C. Teng, S. C. Bearekman, L. B. Turnbull, R. S. Alphin, and W. L. Smith, Ear. EP 0237281  (1987) via Chem. Abstr., 108:21,734f (1988).
  10. ^ Template:Cite DOI
  11. ^ Template:Cite DOI
  12. ^ U.S. patent 5,290,938


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