Studies on the emetic and antiemetic properties of zacopride and its enantiomers.

Abstract

In ferrets, the oral emetic activity of zacopride was compared with its R- and S-enantiomers. Increasing doses of 0.01, 0.1, 1.0, 10.0 and 31.6 mg/kg of zacopride or its 2 enantiomers were each administered at hourly intervals to separate groups of animals until emesis occurred. The emetic (100%) dose for zacopride and its S-enantiomer was 0.11 mg/kg p.o. (cumulative dose). The R-enantiomer at a cumulative dose of 42.71 mg/kg p.o. produced emesis in 25% of the animals. By the i.p. route zacopride and its S-enantiomer were more potent than the R-enantiomer in blocking the emetic activity of 0.1 mg/kg p.o. of zacopride. The involvement of 5-HT3 mechanisms is indicated by a correlation between zacopride and its enantiomers to cause and prevent emesis and their affinity at 5-HT3 binding sites. Further, the putative 5-HT3 agonists, 2-methyserotonin and phenylbiguanide, at 10 mg/kg p.o., produced emesis that was blocked by zacopride (0.1 mg/kg i.p.) or ICS 205-930 (1 mg/kg i.p.). The results suggest that in the ferret the S-enantiomer is predominantly responsible for both the emetic and antiemetic properties of zacopride and that 5-HT3 agonism and antagonism are involved in these actions.

• Authors: L F Sancilio, L M Pinkus, C B Jackson, H R Munson Jr
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 192 Issue 3 Pg. 365-9 (Jan 17 1991) ISSN: 0014-2999 [Print] Netherlands
• PMID: 2055236 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antiemetics
• Benzamides
• Bridged Bicyclo Compounds
• Bridged Bicyclo Compounds, Heterocyclic
• Emetics
• zacopride

Topics

• Administration, Oral
• Animals
• Antiemetics
• Benzamides (pharmacology)
• Bridged Bicyclo Compounds (pharmacology)
• Bridged Bicyclo Compounds, Heterocyclic
• Emetics
• Ferrets
• Male
• Stereoisomerism