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 [11C]methyl ester ([11C]L-NAME) using positron emission tomography in monkey and high performance liquid chromatography methods in dogs and rats. We found that [11C]L-NAME was rapidly (t1/2 = 2 min) metabolized into N omega-nitro-L-arginine (L-NA) and [11C]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.