DOMPERIDONE, A SPECIFIC INVITRO DOPAMINE ANTAGONIST, DEVOID OF INVIVO CENTRAL DOPAMINERGIC ACTIVITY

When tested in different in vitro binding assays and in dopamine-sensitive adenylate cyclase, domperidone was found to be a very potent and specifie dopamine antagonist. Accordingly, [3H]ldomperidone binding sites were exclusively detected in homogenates of brain dopaminergic regions. Despite its powerful dopamine antagonism, domperidone did not act centrally in a similar way to neuroleptic drugs. Ex vivo and in vivo experiments indicated that domperidone is unable to reach dopamine receptors in rat striatum. The very low amount of labelling and atypical distribution found in rat brain after administration of [3H]ldomperidone is compatible with a lack of penetration into brain structures. Finally, domperidone did not elicit marked HVA increase as is found with classical neuroleptic drugs and metoclopramide. From the present experiments, one may conclude that domperidone, though a very potent and specific dopamine antagonist, cannot readily cross the blood brain barrier, which thus prevents the occurrence of central effects. © 1979.