HALOPERIDOL INHIBITS NEURONAL NITRIC-OXIDE SYNTHASE ACTIVITY BY PREVENTING ELECTRON-TRANSFER

The effect of a neuroleptic, haloperidol (HP), on nitric oxide formati on catalyzed by neuronal nitric oxide synthase (n-NOS) in the porcine brain was investigated. HP inhibited n-NOS activity noncompetitively v ersus L-arginine as a substrate, decreasing the maximal velocity (Ki v alue for HP = 31 mu M). HP also inhibited the CaM-dependent NADPH cons umption by n-NOS (IC50 = 221 mu M). These data demonstrate the possibi lity that HP may mediate some neuronal functions through inhibiting NO release by preventing either the electron transfer through n-NOS or t he formation of the activated reduced species of oxygen necessary for the formation of citrulline. And an interaction of HP with CaM may pos sibly affect the consumption of NADPH and n-NOS enzyme activity.