Pharmacological properties of Y-516, a new antipsychotic drug

Iminodibenzy1 derivatives have been prepared in our laboratories for development as psychotropic drugs. Among them, carpipramine (CPP) and clocapramine (CCP) have already been introduced for clinical use as neuroleptic drugs. In the present study, the pharmacological properties of Y-516, which also has an iminodibenzy1 nucleus, were compared with those of CPP, CCP, chlorpromazine (CPZ), haloperidol and sulpiride (SPR). Y-516 inhibited apomorphine (0.5 mg/kg s.c.)-induced hyperactivity in mice, apomorphine (1.25 mg/kg i.v.)-induced gnawing behavior in rats, methamphetamine (2 mg/kg s.c.)-induced hyperactivity in mice and methamphetamine (50 mg/kg i.ρ.)-induced mortality in grouped mice. Except for SPR,the other drugs tested also had similar inhibitory activity. Y-516 was more potent than CCP,but slightly less potent than CPZ in these tests. The antagonistic effect of Y-516 on apomorphine (0.1 mg/kg s.c.)-induced vomiting in dogs was 7 times more potent than that of CPZ. The other drugs tested also showed antagonistic activity in this test. Y-516 antagonized apomorphine (10 mg/kg s.c.)-induced hypothermia in mice. CPZ, on the other hand, potentiated this effect. When combined with methamphetamine (5 mg/kg i.p.) in rats, Y-516 did not induce mortality, but CPP and SPR did. From these results, it would appear that the central antidopaminergic activity of Y-516 differs from that of the other drugs tested.