Systematic (IUPAC) name
Clinical data
Legal status
CAS number  YesY
ATC code None
IUPHAR ligand
ChemSpider  N
Chemical data
Formula C15H20ClN3O2 
Mol. mass 309.791 g/mol

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]


  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.