Chemistry:Minaprine

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Minaprine (INN, USAN, BAN), 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a monoamine oxidase inhibitor antidepressant drug that was used in France for the treatment of depression until it was withdrawn from the market in 1996 because it caused convulsions.[1][2][3][4][5]

Pharmacology

Pharmacodynamics

Minaprine is a monoamine oxidase inhibitor (MAOI).[3] A study found that it acts as a reversible inhibitor of MAO-A (RIMA) in rats, albeit with very low potency.[3][6] In addition to its RIMA activity, minaprine has been found to act as a weak antagonist of the serotonin 5-HT2B receptor (Ki = 863 nM).[7]

It has also been found to weakly inhibit acetylcholinesterase in rat brain (striatum) homogenates.[8]

It has demonstrated significant antibiotic activity against M. chelonae and M. abscessus in tests with antibiotic resistant bacteria.[9]

Chemistry

Synthesis

The first synthesis of minaprine was disclosed in patents published in 1979.[10]

The final step is the reaction between a chloro-substituted pyridazine and the primary amine group of a morpholine derivative.[10][11] 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.[4]

Analogues

Close analogues of minaprine acting as selective serotonin 5-HT2B receptor antagonists such as MW071 and MW073 have been described.[12][13]

References

  1. ↑ Elks, J. (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 826. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA826. Retrieved 9 June 2026. 
  2. ↑ Index Nominum: International Drug Directory. CRC Press. 2004. ISBN 978-3-88763-101-7. https://books.google.com/books?id=EgeuA47Ocm4C&pg=PA808. Retrieved 9 June 2026. 
  3. ↑ 3.0 3.1 3.2 "Minaprine, a new drug with antidepressant properties". Drugs Exp Clin Res 11 (12): 831–840. 1985. PMID 3836113. 
  4. ↑ 4.0 4.1 "3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities". Journal of Medicinal Chemistry 32 (3): 528–537. March 1989. doi:10.1021/jm00123a004. PMID 2563772. 
  5. ↑ "Evaluation of the Characteristics of Safety Withdrawal of Prescription Drugs from Worldwide Pharmaceutical Markets-1960 to 1999". Therapeutic Innovation & Regulatory Science 35 (1): 293–317. 1 January 2001. doi:10.1177/009286150103500134. 
  6. ↑ "Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat". Biochemical Pharmacology 35 (6): 973–978. March 1986. doi:10.1016/0006-2952(86)90085-7. PMID 3954800. 
  7. ↑ "Optimized 5-HT2b inhibitors for neuropsychiatric syndromes with cognitive dysfunction". Alzheimers Dement (N Y) 11 (1). 2025. doi:10.1002/trc2.70073. PMID 40151398. 
  8. ↑ "Aminopyridazines as acetylcholinesterase inhibitors". Journal of Medicinal Chemistry 42 (4): 730–741. February 1999. doi:10.1021/jm981101z. PMID 10052979. 
  9. ↑ "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. doi:10.1093/jac/dkr154. PMID 21486854. 
  10. ↑ 10.0 10.1 Henri Laborit, "Pyridazine derivatives in alleviating depressive states", US patent 4169158, issued 1979-09-25, assigned to CM Industries, SA
  11. ↑ "Minaprine". Pharmaceutical Substances. Thieme. https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-13-0154. 
  12. ↑ "The 5HT2b Receptor in Alzheimer's Disease: Increased Levels in Patient Brains and Antagonist Attenuation of Amyloid and Tau Induced Dysfunction". J Alzheimers Dis 98 (4): 1349–1360. 2024. doi:10.3233/JAD-240063. PMID 38578894. 
  13. ↑ "The Highly Selective 5-HT2B Receptor Antagonist MW073 Mitigates Aggressive Behavior in an Alzheimer's Disease Mouse Model". Cells 15 (3): 273. February 2026. doi:10.3390/cells15030273. PMID 41677635. 



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