Metapramine

Overview

Metapramine is a tricyclic antidepressant (TCA) developed by Rhone Poulenc that was introduced for the treatment of depression in France in 1984. In addition to its efficacy against affective disorders, it also has analgesic properties, and may be useful in the treatment of pain.

Metapramine
Clinical data
Trade namesProdastene, Timaxel
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life7–8 hours
Identifiers
  • (rac)-10,11-dihydro-N,5-dimethyl-5H-dibenz[b,f]azepin-10-amine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC16H18N2
Molar mass238.334 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • CNC1CC2=C(C=CC=C2)N(C)C3=CC=CC=C31

Metapramine (brand names Prodastene, Timaxel) is a tricyclic antidepressant (TCA) developed by Rhone Poulenc[1] that was introduced for the treatment of depression in France in 1984.[2][3] In addition to its efficacy against affective disorders, it also has analgesic properties,[4][5] and may be useful in the treatment of pain.

Metapramine has desipramine-like effects, acting as a norepinephrine reuptake inhibitor without affecting the reuptake of serotonin or dopamine.[6][7][8] It has also been shown to act as a low-affinity NMDA receptor antagonist.[9] Metapramine's direct effects on serotonin, histamine, and muscarinic acetylcholine receptors have not been assayed, but uniquely among most TCAs, it has anecdotally been reported to lack anticholinergic effects.[8][10]

Synthesis

A pair of syntheses has been reported in the patent literature:[11][1]

The hydroboration between iminostilbene (1) and N,N-diethylaminoborane (2) gives 10-borohydro-5-methyl-10,11-dihydro-dibenzo[b,f]azepine (3). This is treated with methylchloramine (4), completing the synthesis of metapramine (5).

References

  1. 1 2 US 3622565, Fouche JC, Alexandre CG, "Dibenzazepine derivatives and their preparation", issued 23 November 1971, assigned to Rhone Poulenc SA
  2. ↑ Dictionary of organic compounds. London: Chapman & Hall. 1996. p. 13. ISBN 0-412-54090-8.
  3. ↑ Vela JM, Buschmann H, Holenz J, Párraga A, Torrens A (2007). "Compounds launched in single countries". Antidepressants, Antipsychotics, Anxiolytics: From Chemistry and Pharmacology to Clinical Application. Weinheim: Wiley-VCH. p. 248. ISBN 978-3-527-31058-6.
  4. ↑ Michael-Titus A, Costentin J (December 1987). "Analgesic effects of metapramine and evidence against the involvement of endogenous enkephalins in the analgesia induced by tricyclic antidepressants". Pain. 31 (3): 391–400. doi:10.1016/0304-3959(87)90167-9. PMID 2827090. S2CID 39569622.
  5. ↑ Fialip J, Marty H, Aumaitre O, Bougerolle AM, Dordain G, Berger JA, Eschalier A (1992). "Antinociceptive activity of metapramine in mice. Relationship with its pharmacokinetic properties". Life Sciences. 50 (3): 161–168. doi:10.1016/0024-3205(92)90268-T. PMID 1731171.
  6. ↑ Dagonneau H, Fonlupt P, Pacheco H (1986). "[Effects, in rats, of metapramine and carpipramine on the uptake of catecholamines and serotonin; relationship with 3H-imipramine binding]". Comptes Rendus des Séances de la Société de Biologie et de Ses Filiales (in French). 180 (1): 43–48. PMID 3017518.
  7. ↑ Warter JM, Tranchant C, Marescaux C, Depaulis A, Lannes B, Vergnes M (1990). "Immediate effects of 14 non MAOI antidepressants in rats with spontaneous petit mal-like seizures". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 14 (2): 261–270. doi:10.1016/0278-5846(90)90106-q. PMID 2106711. S2CID 8332732.
  8. 1 2 Bonierbale M, Dufour H, Scotto JC, Sutter JM (1976). "[Metapramine: antidepressant and psycho-stimulant]". L'Encephale (in French). 2 (3): 219–223. PMID 1033059.
  9. ↑ Boireau A, Bordier F, Durand G, Doble A (1996). "The antidepressant metapramine is a low-affinity antagonist at N-methyl-D-aspartic acid receptors". Neuropharmacology. 35 (12): 1703–1707. doi:10.1016/S0028-3908(96)00122-0. PMID 9076749. S2CID 7244740.
  10. ↑ Dufour P, Billa JP, Fabre J, Roquebert J (1989). "[Evaluation of the central anticholinergic activity of antidepressants. Comparison of two experimental methods]". Annales Pharmaceutiques Françaises (in French). 47 (3): 135–141. PMID 2634929.
  11. ↑ Linares Hubert, GB1323219 (1973 to Rhone-poulenc S.a., Paris).

Related

No related data.

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