Ro 22-1319, a novel pyrroloisoquinoline compound, was identified as a potential
antipsychotic agent in a rat discrete avoidance procedure that is highly specific for such agents. Results in this test are highly correlated with the clinical potency of all types of
antipsychotic agents. The avoidance-blocking potency of
Ro 22-1319 (0.7 mg/kg) in this procedure approached that of
haloperidol (0.4 mg/kg) and was 7- and 12-times greater than that of
chlorpromazine and
clozapine, respectively.
Ro 22-1319 exhibited similar high potency in other rat and monkey avoidance procedures, rat motor activity, and antagonism of
apomorphine emesis in dogs. High potency and
antipsychotic-like activity have been demonstrated in monkey EEG and in an in vivo 3H-spiroperidol binding assay. Although studies of
amphetamine antagonism in rats indicate antidopaminergic activity at nigrostriatal sites,
Ro 22-1319 exhibited relatively weaker cataleptogenic and antistereotypic activity than
haloperidol, and had minimal activity in a rat chronic stereotypy model of receptor supersensitivity. This profile suggests that
Ro 22-1319 is an efficacious
antipsychotic compound, almost as potent as
haloperidol, with fewer or less intense extrapyramidal effects and low potential for
tardive dyskinesia.