IN-VIVO METABOLITES OF N-OMEGA-NITRO-L-ARGININE METHYL-ESTER - METHANOL AND N-OMEGA-NITRO-L-ARGININE

N-omega-nitro-L-arginine methyl ester (L-NAME) is commonly used as a selective inhibitor for in vivo studies of brain nitric oxide (NO) synthase. We aimed to study the fate of N-omega-nitro-L-arginine [C-11]methyl ester ([C-11]L-NAME) using positron emission tomography in monkey and high performance liquid chromatography methods in dogs and rats. We found that [C-11]L-NAME was rapidly (t(1/2) = 2 min) metabolized into N-omega-nitro-L-arginine (L-NA) and [C-11]methanol which both had a slow rate of elimination. Although, in vivo, L-NAME administration leads to long-lasting NO synthase inhibition by L-NA, methanol which is a potent neurotoxin in primate may produce detrimental effects unrelated to NO synthase inhibition.