Haloperidol inhibits neuronal nitric oxide synthase activity by preventing electron transfer

The effect of a neuroleptic, haloperidol (HP), on nitric oxide formation catalyzed by neuronal nitric oxide synthase (n-NOS) in the porcine brain was investigated. HP inhibited n-NOS activity noncompetitively versus L-arginine as a substrate, decreasing the maximal velocity (Ki value for HP = 31 mic...

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Published inNeuropsychobiology Vol. 33; no. 2; p. 76
Main Authors Iwahashi, K, Yoneyama, H, Ohnishi, T, Nakamura, K, Miyatake, R, Suwaki, H, Hosokawa, K, Ichikawa, Y
Format Journal Article
LanguageEnglish
Published Switzerland 01.01.1996
Subjects
Animals
Arginine - pharmacology
Brain - drug effects
Dose-Response Relationship, Drug
Haloperidol - pharmacology
NADP - drug effects
Nitric Oxide Synthase - drug effects
Swine
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Summary:The effect of a neuroleptic, haloperidol (HP), on nitric oxide formation catalyzed by neuronal nitric oxide synthase (n-NOS) in the porcine brain was investigated. HP inhibited n-NOS activity noncompetitively versus L-arginine as a substrate, decreasing the maximal velocity (Ki value for HP = 31 microM). HP also inhibited the CaM-dependent NADPH consumption by n-NOS (IC50 = 221 microM). These data demonstrate the possibility that HP may mediate some neuronal functions through inhibiting NO release by preventing either the electron transfer through n-NOS or the formation of the activated reduced species of oxygen necessary for the formation of citrulline. And an interaction of HP with CaM may possibly affect the consumption of NADPH and n-NOS enzyme activity.
ISSN:0302-282X
DOI:10.1159/000119253