Differential interactions of traditional and novel antiemetics with dopamine D2 and 5-hydroxytryptamine3 receptors

Abstract

The affinities of 11 drugs for both dopamine D2 and 5-hydroxytryptamine3 (5-HT3) receptor sites were determined in brain membranes. The five "traditional" antiemetics (chlorpromazine, prochlorperazine, droperidol, fluphenazine, and domperidone) displayed high affinity (less than 20 nM) for dopamine D2 receptors in corpus striatum but were inactive at 5-HT3 receptors. In contrast, five recently developed 5-HT3 antagonists (BRL 43694, ICS 205-930, zacopride, Lilly 278584, and MDL 72222) displayed nanomolar affinity for the 5-HT3 site but were inactive (greater than 10,000 nM) at the dopamine D2 receptor. Metoclopramide was unique among these agents in that it was similarly potent at dopamine D2 (240 +/- 60 nM) and 5-HT3 (120 +/- 30 nM) receptors.