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Methoxyphenamine metabolism in rat models of human debrisoquine phenotypes

1985; NRC Research Press; Volume: 63; Issue: 7 Linguagem: Inglês

10.1139/y85-129

1205-7541

Sandipan Roy, E. M. Hawes, G. McKay, John W. Hubbard, Kamal K. Midha,

Malaria Research and Control

The metabolism of the β 2 -adrenoceptor agent methoxyphenamine was investigated in rats of the Lewis and Dark Agouti strains, which are proposed models for human extensive and poor metabolizers of debrisoquine, respectively. Following oral ingestion of 20 mg kg −1 of methoxyphenamine, Dark Agouti excreted, on the average, significantly more methoxyphenamine and less (O-demethylmethoxyphenamine and 5-hydroxymethoxyphenamine in 0- to 24-h urine than Lewis. In contrast, the N-demethylation of methoxyphenamine showed no interphenotype differences between the two strains. It is possible that in rats, the form of cytochrome P-450, which controls the 4-hydroxylation of debrisoquine, may also control the O-demethylation and aromatic 5-hydroxylation of methoxyphenamine.