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• W2000589562 abstract "The H2-receptor antagonists 2-guanidino-4(3-methylaminomethyleneiminophenyl)thiazole DA 4643 and 2-methyl-4(4-isopropylaminomethyleneiminophenyl)imidazole DA 5047 were studied for their interaction with cytochrome P-450 and for their influence on lipid peroxidation in vitro. Their activities were compared to those of cimetidine, ranitidine and tiotidine. The interaction with cytochrome P-450 was investigated by binding studies and determination of the influence on the mono-oxygenase and oxidase activities of cytochrome P-450. The effect of the test compounds on enzymatic (NADPH-induced) and non-enzymatic (ascorbate-induced) lipid peroxidation was estimated using normal and heat-inactivated microsomes. The results indicate that DA 5047 and DA 4643 are weaker inhibitors of cytochrome P-450 compared to cimetidine and tiotidine. Cimetidine, ranitidine, tiotidine and DA 5047 did not have any considerable effect on lipid peroxidation. Compound DA 4643 inhibited both enzymatic and non-enzymatic lipid peroxidation. This activity was apparently not related to inhibition of drug metabolizing enzymes but it is probably due to the anti-oxidant properties of this compound. Les antagonistes du récepteur H2 le guanidino-2(méthylaminométhyléneimino-3 phényl)-4 thiazole DA 4643 et le méthyl-2 (isopropylaminométhyléneimino-4 phényl)-4 imidazole DA 5047 ont été étudiés pour leur interaction avec le cytochrome P-450 et leur influence sur la peroxydation lipidique in vitro. Leur activité est comparée à celle de la cimétidine, la ranitidine et la tiotidine. L'interaction avec le cytochrome P-450 est recherchée par des études de liaison et la détermination de l'influence sur l'activité de la mono-oxygénase et de l'oxydase du cytochrome P-450. L'effet des composés essayés sur la peroxadation lipidique enzymatique (induite par le NADPH) et non-enzymatique (induit epar l'ascorbate) est évalué sur des microsomes normaux et inactivés par la chaleur. Les résultats indiquent que les DA 5047 et DA 4643 sont de plus faibles inhibiteurs du cytochrome P-450 comparés à la cimétidine et la tiotidine. Ces deux derniers, de même que la ranitidine et le DA 5047 n'ont pas d'effet considérable sur la peroxydation lipidique. Le composéDA 4643 inhibe à la fois la peroxydation lipidique enzymatique et non-enzymatique. Apparemment, cette activité n'est pas liée à l'inhibition des enzymes métabolisantes mais est probablement due aux propriétés anti-oxydantes du composé." @default.
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• W2000589562 title "The effect of some H2-receptor antagonists on rat hepatic microsomal cytochrome P-450 and lipid peroxidation in vitro" @default.
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• W2000589562 doi "https://doi.org/10.1016/0223-5234(89)90162-1" @default.
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