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.