In vivo metabolites of [formula omitted] methyl ester: methanol and [formula omitted

Abstract

N ω- 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 ω- nitro- L-arginine [ 11C]methyl ester ([ 11C] L-NAME) using position emission tomography in monkey and high performance liquid chromatography methods in dogs and rats. We found that [ 11C] L-NAME was rapidly t 1 2 = 2 min ) metabolized into N ω- 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.