Mammalian Degradation of (-)-Nicotine to 3-Pyridylacetic Acid and Other Compounds.

Abstract

The pattern of urinary excretion of C14 in the dog following intravenous administration of ([long dash])-nicotine-C14 has been examined chromato-graphically by improved procedures. The fractionated urine showed C14 activity corresponding chromatographically to the known metabolites: cotinine, gamma-(3-pyridyl)-gamma-methylaminobutyric acid, desmethylcotinine-hydroxycotinine, and gamma-(3-pyridyl)-[beta]-oxo-N-methylbutyramide. Among many unidentified radioactive components, the urine contained material corresponding chromatographically to 3-pyridylacetic acid. Following oral administration of ([long dash])-cotinine to the dog, 3-pyridylacetic acid was isolated from urine and characterized by analysis, melting point, mixed melting point and as its picric acid salt. A precursor of 3-pyridylacetic acid is on formal grounds gamma-(3-pyridyl)-[beta]-oxobutyric acid, derivable from the known metabolite gamma-(3 -pyridy 1) -[beta]-oxo-N-methylbutyramide.