Neuropharmacological mechanisms of emesis. II. Effects of antiemetic drugs on cisplatin-induced pica in rats.

The effects of diphenhydramine, domperidone, ondansetron, and diphenidol on cisplatin-induced pica (i.e., kaolin ingestion) in rats as the measure analogous to emesis in other species were examined. Ondansetron (2 mg/kg) and diphenidol (30 mg/kg) inhibited kaolin intake induced by cisplatin (10 mg/kg), but diphenhydramine and domperidone did not. Diphenhydramine and diphenidol have been shown to inhibit kaolin intake induced by double rotation, while domperidone and ondansetron did not, and kaolin intake induced by apomorphine was inhibited by domperidone and diphenidol, but not by diphenhydramine or ondansetron. These observations, together with the present findings, suggest that the emetic pathways through the inner ear (double rotation), chemoreceptor trigger zone (apomorphine) and visceral afferent (cisplatin), are pharmacologically independent and are mediated by histamine H1 receptors, dopamine D2 receptors and serotonin 5-HT3 receptors, respectively. It is conceivable that diphenidol may inhibit the emetic center itself, although the receptor on which it acts is not known.