The effect of antidepressants on ethylmorphine and imipramine N-demethylation in rat liver microsomes.
The effects of single and multiple doses of desipramine, amitriptyline or citalopram on the rat liver microsomal cytochrome P-450 level and on the rate of ethylmorphine and imipramine demethylation in-vitro have been investigated. Desipramine, amitriptyline or citalopram when given to rats as a single dose, did not affect the level of cytochrome P-450 in the liver microsomes, however, there was a tendency towards acceleration of imipramine, and particularly ethylmorphine, demethylation. Prolonged administration of desipramine and citalopram, but not amitriptyline, elevated the microsomal level of cytochrome P-450 and accelerated the rate of ethylmorphine demethylation. All the drugs investigated, when given chronically, inhibited the rate of imipramine demethylation. Since demethylation of ethylmorphine and imipramine in a CO atmosphere was inhibited by ca 90% for the former and only by 58% for the latter, it can be assumed that prolonged administration of the drugs investigated has two different effects on the oxygenase systems in rat liver microsomes: on the one hand they stimulate the cytochrome P450 oxygenase system involved in ethylmorphine demethylation and, on the other, they inhibit the other microsomal oxygenase system involved in demethylation of imipramine.
Daniel
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Melzacka
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D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003640:Dealkylation; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism*; D005557:Formaldehyde / Q000378:metabolism; D007099:Imipramine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000928:Antidepressive Agents; D005557:Formaldehyde; D003577:Cytochrome P-450 Enzyme System; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase; D007099:Imipramine