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5332013 
Technical Report 
The Biotransformation Of Nikethamide In The Rat And Its Acceleration By Hexachlorocyclohexane 
Portig, J; Koransky, W; Wahner-Roedler, D 
1972 
274 
2 
The biotransformation of nikethamide (59267), and its acceleration by hexachlorocyclohexane (58899) (HCH), were assessed in female white-rats. Both in-vitro and in-vivo experiments were conducted to determine isolation and estimation of nicotinic-acid-monoethylamide (4314663); isolation of nikethamide metabolites; identification of nikethamide metabolites; and concentration of nikethamide in various organs. Nicotinic-acid-monoethylamide, nicotinamide (98920), and nikethamide-N-oxide (20165962) were identified, by cocrystallization with authentic carriers, as major products of the biotransformation of tritiated nikethamide in the rat. Nicotinic-acid (59676) was a minor metabolite of the analeptic. Both N-dealkylation and N-oxidation of nikethamide were enhanced in rats given a single intraperitoneal injection of 200 milligrams HCH per kilogram body weight. The beta, gamma, and alpha isomers of HCH were all found to be effective. A convulsive dose of nikethamide given intraperitoneally was ineffective in rats pretreated with HCH. Rats could be made tolerant to nikethamide by daily injections of a convulsive dose of the drug for 4 to 5 days. Animals treated as such metabolized nikethamide faster than did non tolerant animals. The authors conclude that desethylation and N-oxidation of nikethamide are detoxifying reactions in that through them the molecule loses its central nervous system excitant properties.