SPECIES-DIFFERENCE IN METABOLISM OF STRYCHNINE WITH LIVER-MICROSOMES OF MICE, RATS, GUINEA-PIGS, RABBITS AND DOGS

The metabolism of strychnine was studied with hepatic microsomes of rats, mice, guinea pigs, rabbits and dogs, using high-performance liquid chromatography. Eight metabolites were found by the incubation with rabbit liver microsomes. Five of them were identified as strychnine N-oxide (St N-oxide), 2-hydroxystrychnine (2-OH St), strychnine 21,22-epoxide, 16-hydroxystrychnine (16-OH St) and 18-oxostrychnine by comparing the chromatographic and spectral data to those of authentic samples. Significant differences in metabolic profiles of strychnine were observed among the above species. The main metabolite in rats and mice was 16-OH St, while in guinea pigs and rabbits, and in dogs, it was 2-OH St, and St N-oxide, respectively. The metabolic activity in guinea pig liver microsomes was much higher than those of other species. There seems to be a fairly good inverse correlation between the metabolic activity and strychnine toxicity in guinea pigs and other animal species. © 1990, The Pharmaceutical Society of Japan. All rights reserved.