title: Haloperidol inhibits neuronal nitric oxide synthase activity by preventing electron transfer.
abstract: 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.
authors.affiliation: Department of Neuropsychiatry, University Hospital, Kagawa Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Iwahashi
authors.forename: H
authors.initials: H
authors.lastname: Yoneyama
authors.forename: T
authors.initials: T
authors.lastname: Ohnishi
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: R
authors.initials: R
authors.lastname: Miyatake
authors.forename: H
authors.initials: H
authors.lastname: Suwaki
authors.forename: K
authors.initials: K
authors.lastname: Hosokawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ichikawa
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D009249:NADP / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000187:drug effects*; D013552:Swine
chemical_list: D009249:NADP; D001120:Arginine; D019001:Nitric Oxide Synthase; D006220:Haloperidol