Piracetam Interactions with Neuroleptics in Psychopharmacological Tests

Two psychopharmacological tests which usually predict neuroleptic activity were conducted after joint administration of piracetam and three neuroleptics (haloperidol, fluphenazine and sulpiride) chosen for their different chemical classes and dopaminergic affinities. In these tests, specific doses of the neuroleptics were used to determine whether piracetam induced potentiation or antagonism of their action. Overall, piracetam increased neuroleptic action regardless of the administration timetable used, but the interaction of fluphenazine differed from that of the other two substances, because piracetam did not modify its action in a specific test of the presynaptic DA-2 dopaminergic receptors. This variation for fluphenazine may be explained by the fact that its pK_a value is closer to that of piracetam, thus preventing better bioavailability of the neuroleptic, or its better affinity for DA-1 dopaminergic receptors. Nevertheless, the variation may have been due to a differing affinity for dopaminergic receptors, although this hypothesis is not completely satisfactory because it does not account for differences due to the administration timetable. It is thus suggested that action occurs on nonspecific sites and has the effect of increasing overall neuroleptic bioavailability.