Increased release of dopamine [formula omitted] by BMY-14802: Contrasting pattern to clozapine

Abstract

In preclinical studies, BMY-14802 [α-(fluorophenyl)-4-(5-fluoro-2-pyramidinyl)-1-piperazine-butanol], a potent sigma ligand, exhibited a profile similar to clozapine, an atyplcal antipsychotic agent. Several atyplcal antipsychotics have previously been demonstrated to increase dopamine (DA) metabolism without altering DA release in vivo , suggesting a potential mechanism for their lack of extrapyramidal side effects. BMY-14802 increased DA metabolism and release while clozapine increased DA metabolism but decreased DA release in the mouse. This is the first demonstration of a sigma ligand mediated DA release in vivo . The lack of extrapyramidal side effects, despite the enhanced DA release in vivo after BMY-14802 suggests that the atyplcal profile of clozapine can not be explained by its depressant actions on DA release alone.