JL13, A PYRIDOBENZOXAZEPINE COMPOUND WITH POTENTIAL ATYPICAL ANTIPSYCHOTIC ACTIVITY: A REVIEW OF ITS BEHAVIOURAL PROPERTIES

The search for an improved clozapine-like compound has resulted in the selection of a new molecule: JL13 (5-(4-methylpiperazin-1-yl)-8-ch loro-pyrido[2,3-b][1,5]benzoxazepine fumarate). Like clozapine, JL13 did not antagonize apomorphine-induced stereotypy and did not produce catalepsy but antagonized apomorphine-induced climbing in rodents (ID50=3.9 mg kg-1s.c.). It was inactive againstd-amphetamine-induced stereotypy but antagonizedd-amphetamine-induced hyperactivity in the mouse (ID50=4.4 mg kg-1i.p.). JL13, like clozapine, was able to antagonize (∓)-DOI-induced head-twitches in the mouse (ID50=2.0 mg kg-1i.p.). In the open-field test in the rat and forced swimming test in the mouse a high similarity was noted between the two drugs in the same range of doses. In a complex temporal regulation schedule in the dog, JL13 showed a high resemblance with clozapine without inducing sialorrhea, palpebral ptosis or any significant motor side effects. In rats trained to discriminate clozapine, JL13 (10 mg kg-1i.p.) induced a high level of generalization (70%) to clozapine. In a drug discrimination procedure in the squirrel monkey, JL13 (3–10 mg kg-1i.m.) produced a full substitution of clozapine. On the basis of these preclinical data, it is thus predicted that JL13 would be a promising atypical antipsychotic drug.