title: Inhibition of monoamine oxidase activity by antidepressants and mood stabilizers.
abstract: OBJECTIVE
  Monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters, has an important role in the brain development and function, and MAO inhibitors have a range of potential therapeutic uses. We investigated systematically in vitro effects of pharmacologically different antidepressants and mood stabilizers on MAO activity.
  
  
  METHODS
  Effects of drugs on the activity of MAO were measured in crude mitochondrial fraction isolated from cortex of pig brain, when radiolabeled serotonin (for MAO-A) or phenylethylamine (for MAO-B) was used as substrate. The several antidepressants and mood stabilizers were compared with effects of well known MAO inhibitors such as moclobemide, iproniazid, pargyline, and clorgyline.
  
  
  RESULTS
  In general, the effect of tested drugs was found to be inhibitory. The half maximal inhibitory concentration, parameters of enzyme kinetic, and mechanism of inhibition were determined. MAO-A was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > desipramine > amitriptyline > imipramine > citalopram > venlafaxine > reboxetine > olanzapine > mirtazapine > tianeptine > moclobemide, cocaine >> lithium, valproate. MAO-B was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > venlafaxine > amitriptyline > olanzapine > citalopram > desipramine > reboxetine > imipramine > tianeptine > mirtazapine, cocaine >> moclobemide, lithium, valproate. The mechanism of inhibition of MAOs by several antidepressants was found various.
  
  
  CONCLUSIONS
  It was concluded that MAO activity is acutely affected by pharmacologically different antidepressants at relatively high drug concentrations; this effect is inhibitory. There are differences both in inhibitory potency and in mechanism of inhibition between both several drugs and the two MAO isoforms. While MAO inhibition is not primary biochemical effect related to their therapeutic action, it can be supposed that decrease of MAO activity may be concerned in some effects of these drugs on serotonergic, noradrenergic, and dopaminergic neurotransmission.
authors.affiliation: Department of Psychiatry, 1st Faculty of Medicine, Charles University, Ke Karlovu 11, 12808 Prague, Czech Republic. zfisar@lf1.cuni.cz
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Fisar
authors.forename: Jana
authors.initials: J
authors.lastname: Hroudová
authors.forename: Jirí
authors.initials: J
authors.lastname: Raboch
mesh_terms: D000339:Affect / Q000187:drug effects*; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018692:Antimanic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology; D015283:Citalopram / Q000494:pharmacology; D003010:Clorgyline / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007490:Iproniazid / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D008803:Mianserin / Q000031:analogs & derivatives / Q000494:pharmacology; D000078785:Mirtazapine; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D020912:Moclobemide / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D000077152:Olanzapine; D010293:Pargyline / Q000494:pharmacology; D000077593:Reboxetine; D013552:Swine; D013841:Thiazepines / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D003511:Cyclohexanols; D008996:Monoamine Oxidase Inhibitors; D009025:Morpholines; D013841:Thiazepines; D005473:Fluoxetine; D015283:Citalopram; C050504:tianeptine; D001569:Benzodiazepines; D000639:Amitriptyline; D008803:Mianserin; D014635:Valproic Acid; D000069470:Venlafaxine Hydrochloride; D000077593:Reboxetine; D008094:Lithium; D010293:Pargyline; D000078785:Mirtazapine; D007490:Iproniazid; D008995:Monoamine Oxidase; D003042:Cocaine; D003010:Clorgyline; D000077152:Olanzapine; D007099:Imipramine; D020912:Moclobemide; D003891:Desipramine