Minaprine

Minaprine
Clinical data
Trade namesBrantur, Cantor, Isopulsan, Nortimic
Other namesAGR-620; AGR620; AGR-1240; AGR1240; CB-30038; CB30038
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
Drug classMonoamine oxidase inhibitor (MAOI); Reversible inhibitor of MAO-A (RIMA)
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances)[1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life2-2.5 hours
Identifiers
  • 4-methyl-N-(2-morpholin-4-ylethyl)-6-phenylpyridazin-3-amine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.043.012
Chemical and physical data
FormulaC17H22N4O
Molar mass298.390 g·mol−1
3D model (JSmol)
  • CC1=CC(=NN=C1NCCN2CCOCC2)C3=CC=CC=C3
  • InChI=1S/C17H22N4O/c1-14-13-16(15-5-3-2-4-6-15)19-20-17(14)18-7-8-21-9-11-22-12-10-21/h2-6,13H,7-12H2,1H3,(H,18,20) Y
  • Key:LDMWSLGGVTVJPG-UHFFFAOYSA-N Y

Minaprine (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, BANTooltip British Approved Name), 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a monoamine oxidase inhibitor antidepressant drug that was used in France for the treatment of depression until it was withdrawn from the market in 1996 because it caused convulsions.[2][3][4][5][6]

Pharmacology

Pharmacodynamics

Minaprine is a monoamine oxidase inhibitor (MAOI).[4] A study found that it acts as a reversible inhibitor of MAO-A (RIMA) in rats, albeit with very low potency.[4][7] 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).[8]

It has also been found to weakly inhibit acetylcholinesterase in rat brain (striatum) homogenates.[9]

It has demonstrated significant antibiotic activity against M. chelonae and M. abscessus in tests with antibiotic resistant bacteria.[10]

Chemistry

Synthesis

The first synthesis of minaprine was disclosed in patents published in 1979.[11]

The final step is the reaction between a chloro-substituted pyridazine and the primary amine group of a morpholine derivative.[11][12] 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.[5]

Analogues

Close analogues of minaprine acting as selective serotonin 5-HT2B receptor antagonists such as MW071 and MW073 have been described.[13][14]

References

  1. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ^ Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 826. ISBN 978-1-4757-2085-3. Retrieved 9 June 2026.
  3. ^ Index Nominum: International Drug Directory. CRC Press. 2004. ISBN 978-3-88763-101-7. Retrieved 9 June 2026.
  4. ^ a b c Bizière K, Worms P, Kan JP, Mandel P, Garattini S, Roncucci R (1985). "Minaprine, a new drug with antidepressant properties". Drugs Exp Clin Res. 11 (12): 831–840. PMID 3836113.
  5. ^ a b Wermuth CG, Schlewer G, Bourguignon JJ, Maghioros G, Bouchet MJ, Moire C, et al. (March 1989). "3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities". Journal of Medicinal Chemistry. 32 (3): 528–537. doi:10.1021/jm00123a004. PMID 2563772.
  6. ^ Fung M, Thornton A, Mybeck K, Wu JH, Hornbuckle K, Muniz E (1 January 2001). "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. doi:10.1177/009286150103500134. S2CID 73036562.
  7. ^ Kan JP, Mouget-Goniot C, Worms P, Biziere K (March 1986). "Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat". Biochemical Pharmacology. 35 (6): 973–978. doi:10.1016/0006-2952(86)90085-7. PMID 3954800.
  8. ^ Roy SM, Acquarone E, Argyrousi EK, Zhang H, Staniszewski A, Inoue A, et al. (2025). "Optimized 5-HT2b inhibitors for neuropsychiatric syndromes with cognitive dysfunction". Alzheimers Dement (N Y). 11 (1) e70073. doi:10.1002/trc2.70073. PMC 11947739. PMID 40151398.
  9. ^ Contreras JM, Rival YM, Chayer S, Bourguignon JJ, Wermuth CG (February 1999). "Aminopyridazines as acetylcholinesterase inhibitors". Journal of Medicinal Chemistry. 42 (4): 730–741. doi:10.1021/jm981101z. PMID 10052979.
  10. ^ Chopra S, Matsuyama K, Hutson C, Madrid P (July 2011). "Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae". The Journal of Antimicrobial Chemotherapy. 66 (7): 1533–1536. doi:10.1093/jac/dkr154. PMID 21486854.
  11. ^ a b US patent 4169158, Henri Laborit, "Pyridazine derivatives in alleviating depressive states", issued 1979-09-25, assigned to CM Industries, SA 
  12. ^ "Minaprine". Pharmaceutical Substances. Thieme. Archived from the original on 2022-12-12. Retrieved 2024-07-21.
  13. ^ Acquarone E, Argyrousi EK, Arancio O, Watterson DM, Roy SM (2024). "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. doi:10.3233/JAD-240063. PMC 11091653. PMID 38578894.
  14. ^ Acquarone E, Roy SM, Staniszewski A, Watterson DM, Arancio O (February 2026). "The Highly Selective 5-HT2B Receptor Antagonist MW073 Mitigates Aggressive Behavior in an Alzheimer's Disease Mouse Model". Cells. 15 (3): 273. doi:10.3390/cells15030273. PMC 12896383. PMID 41677635.
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