EFFECTS OF LONG-TERM TREATMENT WITH DICYCLIC, TRICYCLIC, TETRACYCLIC,AND NONCYCLIC ANTIDEPRESSANT DRUGS ON MONOAMINE-OXIDASE ACTIVITY IN MOUSE-BRAIN

1. The individual long-term effects of the antidepressant drugs zimeld ine, viloxazine, imipramine, amitriptyline, nortriptyline, maprotiline , or nomifensine, on brain mitochondrial monoamine oxidase (MAO) activ ity, were studied in mice that were given daily intraperitoneal inject ions (30 mg/kg) of these reagents for 4 weeks. 2. Both the A-form (MAO -A) and B-form (MAO-B) of MAO were inhibited after long-term administr ation of all the drugs except nortriptyline (MAO-A was not affected) a nd maprotiline (neither MAO-A nor MAO-B were affected). 3. Kinetic ana lysis showed a significant decrease in V-max values, and an increase i n K-m values for MAO-B during treatment. 4. All seven drugs are compet itive inhibitors of MAO-A, noncompetitive inhibitors of MAO-B, and wer e more potent in vitro for MAO-B. 5. MAO-A was inhibited by the follow ing drugs (in ascending order of potency): nortriptyline, amitriptylin e, imipramine, maprotiline, zimeldine, nomifensine, and viloxazine. 6. MAO-B was inhibited by the following drugs (in ascending order of pot ency): nortriptyline, imipramine, maprotiline, amitriptyline, zimeldin e, nomifensine, and viloxazine.