Studies on the emetic and antiemetic properties of zacopride and its enantiomers
| Autor: | H. Randall Munson, Lawrence M. Pinkus, Carlotta B. Jackson, Lawrence F. Sancilio |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Pharmacology
Male medicine.drug_class Chemistry Cumulative dose Ferrets Administration Oral Stereoisomerism Bridged Bicyclo Compounds Heterocyclic Zacopride chemistry.chemical_compound Bridged Bicyclo Compounds Oral administration Benzamides medicine Antiemetic Animals Antiemetics Enantiomer Emetics Phenylbiguanide |
| Zdroj: | European journal of pharmacology. 192(3) |
| ISSN: | 0014-2999 |
| Popis: | 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-methylserotonin 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. |
| Databáze: | OpenAIRE |
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