Effect of trimipramine, an atypical tricyclic antidepressant, on the activities of various enzymes involved in the metabolism of biogenic amines.
1. The mechanism of action of trimipramine, a clinically efficacious tricyclic antidepressant, is not well understood. In order to investigate whether it might affect the activities of different enzymes involved in biogenic amine metabolism we have undertaken a comparative study of it along with amitriptyline. 2. Neither trimipramine nor amitriptyline, at concentrations up to 1 mM, exhibited any significant effect on phenylalanine hydroxylase, tyrosine hydroxylase, L-aromatic amino acid decarboxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyltransferase, catechol-O-methyltransferase, phenylsulfotransferase or tyrosine aminotransferase. 3. Monoamine oxidase, however, was inhibited by both drugs with the greatest effect being on MAO-B. The inhibition was reversible, non-competitive and relatively weak.
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Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.
Boulton
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D000311:Adrenal Glands / Q000201:enzymology; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D015239:Arylsulfotransferase / Q000378:metabolism; D001679:Biogenic Amines / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002417:Cattle; D003984:Dibenzazepines / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D010651:Phenylalanine Hydroxylase / Q000378:metabolism; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014299:Trimipramine / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014444:Tyrosine Transaminase / Q000378:metabolism
D001679:Biogenic Amines; D003984:Dibenzazepines; D000639:Amitriptyline; D014299:Trimipramine; D010651:Phenylalanine Hydroxylase; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D008995:Monoamine Oxidase; D010625:Phenylethanolamine N-Methyltransferase; D002394:Catechol O-Methyltransferase; D014444:Tyrosine Transaminase; D015239:Arylsulfotransferase; D001142:Aromatic-L-Amino-Acid Decarboxylases