In vivo metabolites of Nω-nitro-L-arginine methyl ester: methanol and Nω-nitro-L-arginine

$\text{N}{}^{\mathrm{\omega }}\text{-}\text{nitro-}\text{L}\text{-arginine}$ 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 $\text{N}{}^{\mathrm{\omega }}\text{-}\text{nitro-}\text{L}\text{-arginine}$ [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 $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{= 2}\text{min}$) metabolized into $\text{N}{}^{\mathrm{\omega }}\text{-}\text{nitro-}\text{L}\text{-arginine}$ (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.