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.
Brouillet
E
E
Service Hospitalier Frédéric Joliot, CEA-DRIPP, Orsay, France.
Roeda
D
D
Valette
H
H
Fuseau
C
C
Guyot
M C
MC
Crouzel
C
C
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004285:Dogs; D008297:Male; D000432:Methanol / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D019335:Nitroarginine; D010215:Papio; D051381:Rats
D019335:Nitroarginine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D000432:Methanol