Neurochemical Study of Mafoprazine, a New Phenylpiperazine Derivative

Abstract

Mafoprazine, a phenylpiperazine derivative, was neurochemically investigated in rats to determine its action mechanism. The rank order of affinity of mafoprazine for neuronal receptors was D2≧α1 S2>α2≫D1>βmACh. The affinity of mafoprazine for D2 receptors (Ki=10.7 nM) was 2 times higher than that of azaperone, and 6 and 1 6 times lower than those of chlorpromazine and haloperidol, respectively, whereas the D2 receptor selectivity [D1/D2 (Ki value ratio)] of mafoprazine was 10, 9 and 2 times higher than those of chlorpromazine, azaperone and haloperidol, respectively. The affinity of mafoprazine for α2 receptors in terms of the ratio of the Ki values for D2 and α2 receptors (D2/α2) was 345, 26 and 3 times higher than those of haloperidol, chlorpromazine and azaperone, respectively. Mafoprazine slightly showed the inhibitory effect on dopamine-stimulated adenylate cyclase (IC50 = 52300 nM), and it had almost no affinity for β and mACh receptors. Mafoprazine significantly increased dopamine metabolites in the corpus striatum and nucleus accumbens, although to lesser extents as compared with azaperone and chlorpromazine. These results suggest that mafoprazine probably manifests its antipsychotic action mainly through D2 receptor blocking activity and α-adrenergic activity (α1 receptor blocking activity and α2 receptor stimulating activity).