BINDING CHARACTERISTICS OF REMOXIPRIDE AND ITS METABOLITES TO DOPAMINE-D2 AND DOPAMINE-D3 RECEPTORS

The substituted benzamide, remoxipride, is a new atypical antipsychoti c agent with good clinical efficacy and low extrapyramidal side-effect potential. In the present study, the in vitro receptor binding proper ties of remoxipride and several of its metabolites to rat striatal dop amine D2 and cloned human dopamine D2A and D3 receptors were investiga ted. Remoxipride bound to [H-3]raclopride-labelled dopamine D2 recepto rs in rat striatum with an affinity (K(i)) of 113 nM. The significantl y lower affinities of remoxipride reported when [H-3]spiperone was use d as a radioligand are suggested to be due to methodological problems associated with the use of very high-affinity radioligands. Some of th e phenolic metabolites of remoxipride found mainly in rat exhibited co nsiderably higher affinities to dopamine D2 and D3 receptors than remo xipride itself. The pyrrolidone metabolites found mainly in the human had very low dopamine D2 and D3 affinities. The present in vitro resul ts suggest that the behavioural effects of remoxipride in rats may ref lect the effect of remoxipride and some of its high-affinity metabolit es.