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.