Metapramine

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 [92483-74-4] (1) and N,N-diethylaminoborane (PC13980368) (2) gives 10-borohydro-5-methyl-10,11-dihydro-dibenzo[b,f]azepine (3). This is treated with methylchloramine [6154-14-9] (4) completing the synthesis of metapramine (5).

References

  1. ^ a b 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. ^ a b 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).
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