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We evaluated the inhibitory action of benexate (benzyl 2-[trans-4 -(guanidinomethyl) cyclohexylcarbonyloxy] benzoate hydrochloride beta-cyclodextrin clathrate), an anti-ulcer agent, on the formation of nitric oxide by stomach and brain enzyme preparations and on the purified neuronal nitric oxide synthase (NOS). Benexate markedly inhibited NOS activities of both stomach and brain preparations, with IC50 values of 68 and 29 microM, respectively. The results of double-reciprocal analysis suggested 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 production of hydrogen peroxide by the enzyme. Taken together, it is indicated that benexate is an inhibitor for NOS in spite of the fact the drug elicits an increase in blood flow in a gastric mucosa.
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T Arimoto, and
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T Arimoto, and
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T Arimoto, and
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T Arimoto, and
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Y Kumagai
August 1996,
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T Arimoto, and
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Y Kumagai
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