Minaprine (, , ), sold under the brand name Cantor among others, is a monoamine oxidase inhibitor antidepressant drug that was used in France for the treatment of depression until it was withdrawn from the market in 1996 because it caused convulsions.

Pharmacology

Pharmacodynamics

Minaprine is a monoamine oxidase inhibitor (MAOI). A study found that it acts as a reversible inhibitor of MAO-A (RIMA) in rats, albeit with very low potency. In addition to its RIMA activity, minaprine has been found to act as a weak antagonist of the serotonin 5-HT2B receptor (Ki = 863nM).

It has also been found to weakly inhibit acetylcholinesterase in rat brain (striatum) homogenates.

It has demonstrated significant antibiotic activity against M. chelonae and M. abscessus in tests with antibiotic resistant bacteria.

Chemistry

Synthesis

The first synthesis of minaprine was disclosed in patents published in 1979.

The final step is the reaction between a chloro-substituted pyridazine and the primary amine group of a morpholine derivative. The required pyridazine can be made by the reaction of acetophenone and pyruvic acid, followed by ring formation using hydrazine, giving a pyrazidinone. Treatment of this with phosphoryl chloride converts it to the required chloro derivative.

Analogues

Close analoguess of minaprine acting as selective serotonin 5-HT2B receptor antagonistss such as MW071 and MW073 have been described.

References