INHIBITION OF CONSTITUTIVE NITRIC-OXIDE SYNTHASE BY BENEXATE

We evaluated the inhibitory action of benexate (benzyl 2-[trans-4-(gua nidinomethyl) cyclohexylcarbonyloxy] benzoate hydrochloride beta-cyclo dextrin clathrate), an anti-ulcer agent, on the formation of nitric ox ide by stomach and brain enzyme preparations and on the purified neuro nal nitric oxide synthase (NOS). Benexate markedly inhibited NOS activ ities of both stomach and brain preparations, with IC50 values of 68 a nd 29 mu M, respectively. The results of double-reciprocal analysis su ggested that the inhibition was competitive with an arginine substrate . Experiments with purified NOS revealed that benexate suppressed not only citrulline formation but also the oxidation of NADPH and the prod uction of hydrogen peroxide by the enzyme. Taken together, it is indic ated that benexate is an inhibitor for NOS in spite of the fact the dr ug elicits an increase in blood flow in a gastric mucosa.