A dual effect of some 5-HT3 receptor antagonists on cisplatin-induced emesis in the pigeon.

Abstract:

: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.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Navarra P,Martire M,del Carmine R,Pozzoli G,Preziosi P

doi

10.1016/0378-4274(92)90256-j

keywords:

subject

Has Abstract

pub_date

1992-12-01 00:00:00

pages

745-9

eissn

0378-4274

issn

1879-3169

pii

0378-4274(92)90256-J

journal_volume

64-65 Spec No

pub_type

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