CHLORPROMAZINE REDUCES TOXICITY AND CA2-BETA PROTEIN (25-35) IN-VITRO( UPTAKE INDUCED BY AMYLOID)

Amyloid beta protein (AP), has been reported to be toxic to neurons in vitro. However, the molecular mechanism leading to neuronal death rem ains unknown. Here we report protective effects of phenothiazines, a c lass of neuroleptic agent, against A beta toxicity in primary cultures of rat cortical neurons and PC12 cells. beta(25-35), an active sequen ce of A beta, showed dose-dependent reduction of the 3-(4,5-dimethylth iazol-2-yl)-2,5-diphenyl tetrazolium bromide dye (MTT) reductivity, an d chlorpromazine (CPZ), promethazine or trifluoperazine restored it at micromolar concentration. The significant increase in Ca2+ uptake by chronic treatment of beta(25-35) was reduced not only by nimodipine bu t also by CPZ. These results suggest that phenothiazines attenuate bet a(25-35) toxicity possibly by reducing of Ca2+ influx through L-type C a2+ channels.