Pharmacokinetic aspects of the mode of action of EGYT-475, a new antidepressant agent.
EGYT-475 (N-benzyl-piperazine-picolinyl fumarate; Trelibet) metabolism was compared in rats, dogs and man. In the rat 7 urinary metabolites of EGYT-475 were found, and 4 were identified as: N-picolinyl-piperazine (EGYT-1354) (30%), picolinic acid (28.5%), hippuric acid (53%) and N-benzylpiperazine (EGYPT-2760) (3.7%). The results show that debenzylation is the main route of EGYT-475 metabolism in the rat. By this route EGYT-2760, the active EGYT-475 metabolite, is further metabolized. In the dog the main metabolic pathway is hydrolysis, and because of that the formed EGYT-2760 is not metabolized further and its urinary content exceeds 50%. In man, similarly as in the rat, debenzylation is the preferred route of EGYT-475 metabolism. These results explain much higher toxicity of EGYT-475 in dogs than in rats and man.
Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
K
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Magyar
D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D066298:In Vitro Techniques; D010879:Piperazines / Q000493:pharmacokinetics* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013574:Synaptosomes / Q000378:metabolism
D000928:Antidepressive Agents; D010879:Piperazines; C040401:EGYT 475