Minaprine is an amino-phenylpyridazine antidepressant. It is indicated in the treatment of various depressive states. Minaprine acts on many targets in the neurons. Firstly, this drug binds as an antagonist to the serotonin type 2 receptors (C, B, and C). Secondly, it can also antagonize the dopamine D1 and D2 type receptors. In third place, minaprine binds to the serotonin reuptake pump. With these three actions, minaprine blocks the reuptake of dopamine and serotonin, leaving more of those two neurotransmitters in the synapse. Furthermore, minaprine also acts as a reversible inhibitor of the amine oxidase [flavin-containing] A enzyme. The monoamine oxidase is an enzyme that catalyzes the oxidative deamination of many amines like serotonin, norepinephrine, epinephrine, and dopamine. There are 2 isoforms of this protein: A and B. The first one is found in cells located in the periphery and breakdown serotonin, norepinephrine, epinephrine, dopamine, and tyramine. The second one, the B isoform, breakdowns phenylethylamine, norepinephrine, epinephrine, dopamine, and tyramine. This isoform is found in the extracellular tissues and mostly in the brain. The mechanism of action of the MAOIs is still not determined, it is thought that they act by increasing free serotonin and norepinephrine (shown in this pathway) concentrations and/or by altering the concentrations of other amines in the CNS. MAO A inhibition is thought to be more relevant to antidepressant activity than the inhibition caused by MAO B. Selective MAO B inhibitors have no antidepressant effects.
Kan JP, Mouget-Goniot C, Worms P, Biziere K: Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat. Biochem Pharmacol. 1986 Mar 15;35(6):973-8. doi: 10.1016/0006-2952(86)90085-7.
Kan JP, Mouget-Goniot C, Worms P, Biziere K: Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat. Biochem Pharmacol. 1986 Mar 15;35(6):973-8. doi: 10.1016/0006-2952(86)90085-7.
Biziere K, Worms P, Kan JP, Mandel P, Garattini S, Roncucci R: Minaprine, a new drug with antidepressant properties. Drugs Exp Clin Res. 1985;11(12):831-40.
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