Alterations induced in distribution and in vivo metabolism of imipramine by pregnenolone-16alpha-carbonitrile.
Female rats were given pregnenolone-16alpha-carbonitrile (I) to investigate its in vivo effects on the loss of the righting reflex and the mortality rate induced by imipramine as well as the concentrations of this drug and its metabolite, desipramine, in plasma, brain, liver, lungs, and kidneys. The protective action of I was associated with diminished organ levels of imipramine (catatoxic mechanism), and the relationship between brain and plasma imipramine concentrations remained unaltered. Desipramine-imipramine molar ratios were increased, indicating an elevated rate of N-demethylation. The unbound imipramine in plasma was diminished, but the relationship between protein-bound and unbound imipramine levels was not modified.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001923:Brain Chemistry; D002849:Chromatography, Gas; D003891:Desipramine / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D007099:Imipramine / Q000097:blood / Q000378:metabolism* / Q000633:toxicity; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D013997:Time Factors
D001798:Blood Proteins; D011285:Pregnenolone Carbonitrile; D007099:Imipramine; D003891:Desipramine