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Synthesis and Biological Evaluation of 1-(1,2-Benzisothiazol-3-yl)- and (1,2-Benzisoxazol-3-yl)piperazine Derivatives as Potential Antipsychotic Agents
Members of the series of title compounds were tested for potential antipsychotic activity in relevant receptor binding assays and behavioral screens.Structure-activity relationships within the series are discussed.Compound 24 (BMY 13859-1), a (1,2-benzisothiazol-3-yl)piperazine derivative, was selected for further study because of its potent and selective profile in primary CNS tests.It was active in the Sidman avoidance paradigm and blocked amphetamine-induced stereotyped behavior in dogs for up to 7 h.The compound’s lack of typical neuroleptic-like effects in therat catalepsy test and its failure to produce dopamine receptor supersensitivity following chronic administration indicate that it should not cause the movement disorders commonly associated with antipsychotic therapy.Although 24 has potent affinity for dopaminergic binding sites, its even greater affinity for serotonin receptors suggests that a serotonergic component may be relevant to its atypical profile.Compound 24 is currently undergoing clinical evaluation in schizophrenic patients.
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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics