Minaprine Explained

Minaprine (INN, USAN, BAN; brand names Brantur, Cantor) 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a monoamine oxidase inhibitor antidepressant drug that was used in France for the treatment of depression until it was withdrawn from the market in 1996 because it caused convulsions.^{[1] [2]}

A study found that it acts as a reversible inhibitor of MAO-A (RIMA) in rats.^[3] It has also been found to weakly inhibit acetylcholinesterase in rat brain (striatum) homogenates.^[4]

It has demonstrated significant antibiotic activity against M. chelonae and M. abscessus in tests with antibiotic resistant bacteria.^[5]

Synthesis

The first synthesis of minaprine was disclosed in patents published in 1979.^[6]

The final step is the reaction between a chloro-substituted pyridazine and the primary amine group of a morpholine derivative.^{[6] [7]} 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.^[1]

Notes and References

1. Wermuth CG, Schlewer G, Bourguignon JJ, Maghioros G, Bouchet MJ, Moire C, Kan JP, Worms P, Biziere K . 3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities . Journal of Medicinal Chemistry . 32 . 3 . 528–537 . March 1989 . 2563772 . 10.1021/jm00123a004 .
2. Fung M, Thornton A, Mybeck K, Wu JH, Hornbuckle K, Muniz E . Evaluation of the Characteristics of Safety Withdrawal of Prescription Drugs from Worldwide Pharmaceutical Markets-1960 to 1999. Therapeutic Innovation & Regulatory Science. 1 January 2001. 35. 1. 293–317. 10.1177/009286150103500134. 73036562.
3. Kan JP, Mouget-Goniot C, Worms P, Biziere K . Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat . Biochemical Pharmacology . 35 . 6 . 973–978 . March 1986 . 3954800 . 10.1016/0006-2952(86)90085-7 .
4. Contreras JM, Rival YM, Chayer S, Bourguignon JJ, Wermuth CG . Aminopyridazines as acetylcholinesterase inhibitors . Journal of Medicinal Chemistry . 42 . 4 . 730–741 . February 1999 . 10052979 . 10.1021/jm981101z .
5. Chopra S, Matsuyama K, Hutson C, Madrid P . Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae . The Journal of Antimicrobial Chemotherapy . 66 . 7 . 1533–1536 . July 2011 . 21486854 . 10.1093/jac/dkr154 . free .
6. US . 4169158 . Henri Laborit . Pyridazine derivatives in alleviating depressive states . patent . 1979-09-25 . 1977-07-29 . CM Industries, SA.
7. Web site: Minaprine . Pharmaceutical Substances . Thieme . 2024-07-21 .