Navarra P, Martire M, del Carmine R, Pozzoli G, Preziosi P
Department of Pharmacology, Catholic University Medical School, Rome, Italy.
Toxicol Lett. 1992 Dec;64-65 Spec No:745-9. doi: 10.1016/0378-4274(92)90256-j.
In the present study, the emetic effect of the anticancer drug cisplatin, and protective effects of 5-HT3 receptor antagonists against cisplatin emesis were investigated in the pigeon. The experimental setting involved the i.v. administration of drugs and subsequent observation of the percentage of vomiting animals and number of emetic episodes per vomiting animal over a period of 5 h. In some experiments, the 5-HT and 5-HIAA content in tissues was estimated by the HPLC technique. It was observed that cisplatin (2.5-10 mg/kg) is able to induce dose-dependent emesis in the pigeon. 5-HT3 receptor antagonists (500 micrograms/kg) afford partial protection against cisplatin emesis, although some of them, i.e. indolic derivatives and zacopride, display intrinsic emetic activity at doses of 50-500 micrograms/kg. 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 (300 mg/kg x 3 days), is able to hamper vomiting induced by either cisplatin or 5-HT3 receptor antagonists. It is concluded that the intrinsic emetic effects of 5-HT3 receptor antagonists in the pigeon provide pharmacological evidence of species differences in the properties of 5 HT3 receptors.
在本研究中，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在5小时内的呕吐发作次数。在一些实验中，通过高效液相色谱（HPLC）技术估算组织中的5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）含量。观察到顺铂（2.5 - 10毫克/千克）能够在鸽子身上诱导剂量依赖性呕吐。5-HT3受体拮抗剂（500微克/千克）对顺铂所致呕吐提供部分保护，尽管其中一些，即吲哚衍生物和扎考必利，在50 - 500微克/千克剂量时表现出内在催吐活性。一种5-羟色胺能机制似乎参与了顺铂和5-HT3受体拮抗剂所致的呕吐，因为用5-羟色胺合成抑制剂对氯苯丙氨酸（300毫克/千克×3天）预处理能够抑制顺铂或5-HT3受体拮抗剂所致的呕吐。得出的结论是，5-HT3受体拮抗剂在鸽子身上的内在催吐作用为5-HT3受体特性的种属差异提供了药理学证据。
