Ｉｍｉｎｏｄｉｂｅｎｚｙｌ系化合物，Ｙ‐５１６の行動薬理学的研究

Abstract

Iminodibenzyl derivatives have been prepared in our laboratories for development as psychotropic drugs. Among them, carpipramine and clocapramine have already been introduced for clinical use as neuroleptic drugs. In the present study, the pharmacological properties of Y-516, a new iminodibenzyl derivative, were compared with those of carpipramine, clocapramine, haloperidol and sulpiride. Y-516 inhibited apomorphine (0.5 mg/kg, s.c.)-induced hyperactivity in mice, apomorphine (10 mg/kg, s.c.)-induced hypothermia in mice, apomorphine (0.1 mg/kg, s.c.)-induced vomiting in dogs, methamphetamine (2 mg/kg, s.c.)-induced hyperactivity in mice and methamphetamine (50 mg/kg, i.p.)-induced mortality in grouped mice. Y-516 also suppressed both lateral hypothalamic self-stimulation behavior in rats and circling behavior induced by methamphetamine (5 mg/kg, i.p.) in rats with unilateral 6-hydroxydopamine lesions of the striatum. In these tests, Y-516 was 2--3 times more potent than clocapramine, but less potent than haloperidol. The inhibitory effect of Y-516 on apomorphine (1.25 mg/kg, i.v.)-induced gnawing behavior in rats was slightly more potent than that of clocapramine. Y-516 in combination treatment with methamphetamine (5 mg/kg, i.p.) did not induce mortality in rats; however, carpipramine and sulpiride did. The cataleptogenic action of Y-516 was almost equipotent to that of clocapramine. From these results, Y-516 possesses a post-synaptic dopamine receptor blocking action similar to that of the iminodibenzyl antipsychotic drugs, suggesting its potential usefulness as an antipsychotic drug.