Bhandari P, Bingham S, Andrews P L
Department of Physiology, St George's Hospital Medical School, London, U.K.
Neuropharmacology. 1992 Aug;31(8):735-42. doi: 10.1016/0028-3908(92)90034-m.
Loperamide, an opiate receptor agonist, commonly used in the treatment of diarrhoea, reliably induced emesis in the ferret, when given subcutaneously. The response latency was short (less than 10 min) and the emesis lasted for approx 70 min. The dose-response curve for the emetic response was "bell-shaped" and all animals responded at 0.5 mg/kg but none at 5 mg/kg (s.c.). The response was unaffected by dopamine D2 receptor antagonism (domperidone 1.0 mg/kg, s.c.) or 5-HT3 receptor antagonism (granisetron or ondansetron 1.0 mg/kg, s.c.). The onset of the response was delayed for about 60 min by naloxone or naloxone methiodide (1.0 mg/kg, s.c.) and abolished by naloxanazine (1.0 mg/kg, s.c.), reported to be relatively selective for mu receptors. The results implicate mu receptors (possibly mu 1) in the induction of emesis by loperamide and provide some support for activation of opiate receptors also having anti-emetic effects, as suggested in previous studies. The emetic response to loperamide was unaffected by abdominal vagotomy but was abolished by ablation of the area postrema, indicating that loperamide-induced emesis may be used as a test for ablation of the area postrema in studies of the emetic mechanism in the ferret.
洛哌丁胺是一种阿片受体激动剂，常用于治疗腹泻，皮下注射时能可靠地诱发雪貂呕吐。反应潜伏期短（不到10分钟），呕吐持续约70分钟。催吐反应的剂量反应曲线呈“钟形”，所有动物在0.5毫克/千克时均有反应，但在5毫克/千克（皮下注射）时无反应。该反应不受多巴胺D2受体拮抗作用（多潘立酮1.0毫克/千克，皮下注射）或5-HT3受体拮抗作用（格拉司琼或昂丹司琼1.0毫克/千克，皮下注射）的影响。纳洛酮或甲基碘化纳洛酮（1.0毫克/千克，皮下注射）使反应 onset 延迟约60分钟，而纳洛嗪（1.0毫克/千克，皮下注射）则消除了该反应，据报道纳洛嗪对μ受体具有相对选择性。结果表明μ受体（可能是μ1）参与了洛哌丁胺诱发呕吐的过程，并为先前研究中提出的阿片受体激活也具有止吐作用提供了一些支持。对洛哌丁胺的催吐反应不受腹部迷走神经切断术的影响，但在最后区被切除后则消失，这表明在雪貂呕吐机制的研究中，洛哌丁胺诱发的呕吐可作为最后区切除的一种测试方法。
