Preziosi P, D'Amato M, Del Carmine R, Martire M, Pozzoli G, Navarra P
Department of Pharmacology, Catholic University School of Medicine, Rome, Italy.
Eur J Pharmacol. 1992 Oct 20;221(2-3):343-50. doi: 10.1016/0014-2999(92)90721-f.
In the present study, the emetic effect of the anticancer drug cisplatin, and the protective effects of 5-HT3 receptor antagonists against cisplatin emesis were investigated in the pigeon. The experimental set-up involved the i.v. administration of drugs and subsequent observation of the percentage of vomiting animals and the number of emetic episodes per vomiting animal. It was observed that cisplatin induced dose-dependent emesis in the pigeon. 5-HT3 receptor antagonists afforded partial protection against cisplatin emesis, although some of them, i.e. indole, indole-like derivatives and zacopride, displayed intrinsic emetic activity. A serotonergic mechanism appears to be involved in both cisplatin- and 5-HT3 receptor antagonist-induced emesis, since pretreatment with an inhibitor of 5-HT synthesis, para-chlorophenylalanine (pCPA), prevented vomiting induced by either cisplatin or 5-HT3 receptor antagonists. It is concluded that the intrinsic emetic effects of 5-HT3 receptor antagonists provide pharmacological evidence of species differences in the properties of 5-HT3 receptors.
在本研究中，我们在鸽子身上研究了抗癌药物顺铂的催吐作用以及5-羟色胺3（5-HT3）受体拮抗剂对顺铂所致呕吐的保护作用。实验设置包括静脉注射药物，随后观察呕吐动物的百分比以及每只呕吐动物的呕吐发作次数。据观察，顺铂在鸽子身上引起剂量依赖性呕吐。5-HT3受体拮抗剂对顺铂所致呕吐提供了部分保护作用，尽管其中一些药物，即吲哚、吲哚样衍生物和扎考必利，表现出内在催吐活性。5-羟色胺能机制似乎与顺铂和5-HT3受体拮抗剂所致呕吐均有关，因为用5-羟色胺合成抑制剂对氯苯丙氨酸（pCPA）进行预处理可防止顺铂或5-HT3受体拮抗剂所致的呕吐。得出的结论是，5-HT3受体拮抗剂的内在催吐作用为5-HT3受体特性的种属差异提供了药理学证据。
