Middlefell V C, Price T L
Department of Biomedical Research, Wyeth Research Ltd, Maidenhead, Berkshire, UK.
Br J Pharmacol. 1991 May;103(1):1011-2. doi: 10.1111/j.1476-5381.1991.tb12292.x.
The racemic 5-HT3 receptor antagonist, zacopride (10-100 micrograms kg-1, i.m.) evoked an emetic response in ferrets. This property appeared to reside totally in the S-enantiomer which also produced emesis over the same dose range. This emesis could be prevented by pretreatment with ondansetron (1 mg kg-1, i.m.) or by R-zacopride (100 micrograms kg-1, i.m.). In urethane-anaesthetized ferrets, S-zacopride (0.3 micrograms kg-1, i.v.) evoked a profound Bezold-Jarisch reflex which was blocked by both ondansetron (30 micrograms kg-1, i.v.) and by R-zacopride (100 micrograms kg-1, i.v.). These results suggest that, in the ferret, S-zacopride possesses 5-HT3 receptor agonist properties which may be responsible for the emetic effect. In contrast R-zacopride does not appear to possess 5-HT3 receptor agonist properties in this species.
消旋5-羟色胺3（5-HT3）受体拮抗剂扎考必利（10 - 100微克/千克，肌肉注射）可引起雪貂呕吐反应。此特性似乎完全存在于S-对映体中，该对映体在相同剂量范围内也会引发呕吐。昂丹司琼（1毫克/千克，肌肉注射）预处理或R-扎考必利（100微克/千克，肌肉注射）可预防这种呕吐。在氨基甲酸乙酯麻醉的雪貂中，S-扎考必利（0.3微克/千克，静脉注射）引发强烈的贝佐尔德-雅里什反射，昂丹司琼（30微克/千克，静脉注射）和R-扎考必利（100微克/千克，静脉注射）均可阻断该反射。这些结果表明，在雪貂中，S-扎考必利具有5-HT3受体激动剂特性，这可能是其致吐作用的原因。相比之下，R-扎考必利在该物种中似乎不具有5-HT3受体激动剂特性。
