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Pathway Description
Venlafaxine Metabolism Pathway
Homo sapiens
Drug Metabolism Pathway
Venlafaxine (also named as Effexor or Elafax) is an antidepressant medication, which belongs to the class of serotonin-norepinephrine reuptake inhibitor (SNRI). Venlafaxine is well absorbed into the circulation system. Venlafaxine is also metabolized to N-desmethylvenlafaxine. The N-demethylation is catalyzed by CYP3A4 and CYP2C19. N-desmethylvenlafaxine is a weaker serotonin and norepinephrine reuptake inhibitor. Both O-desmethylvenlafaxine (as potent a serotonin-norepinephrine reuptake inhibitor) and N-desmethylvenlafaxine are further metabolized by CYP2C19, CYP2D6 and/or CYP3A4 to a minor metabolite N,O-didesmethylvenlafaxine that is further metabolized into N,N,O-tridesmethylvenlafaxine or excreted as N,O-didesmethylvenlafaxine gucuronide. Later on, O-desmethylvenlafaxine is exported without any change in chemical structure. Venlafaxine is exported via two transporters: Multidrug resistance protein 1 and ATP-binding cassette sub-family G member 2.
References
Venlafaxine Pathway References
[PharmgKB](http://www.pharmgkb.org/pathway/PA166014758)
Durand JP, Deplanque G, Montheil V, Gornet JM, Scotte F, Mir O, Cessot A, Coriat R, Raymond E, Mitry E, Herait P, Yataghene Y, Goldwasser F: Efficacy of venlafaxine for the prevention and relief of oxaliplatin-induced acute neurotoxicity: results of EFFOX, a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2012 Jan;23(1):200-5. doi: 10.1093/annonc/mdr045. Epub 2011 Mar 22.
Pubmed: 21427067
Grothe DR, Scheckner B, Albano D: Treatment of pain syndromes with venlafaxine. Pharmacotherapy. 2004 May;24(5):621-9.
Pubmed: 15162896
Khalifa M, Daleau P, Turgeon aJ: Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes. J Pharmacol Exp Ther. 1999 Oct;291(1):280-4.
Pubmed: 10490914
Rudolph RL, Fabre LF, Feighner JP, Rickels K, Entsuah R, Derivan AT: A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression. J Clin Psychiatry. 1998 Mar;59(3):116-22.
Pubmed: 9541154
Thase ME: Efficacy and tolerability of once-daily venlafaxine extended release (XR) in outpatients with major depression. The Venlafaxine XR 209 Study Group. J Clin Psychiatry. 1997 Sep;58(9):393-8.
Pubmed: 9378690
Grunder G, Wetzel H, Schlosser R, Benkert O: Subchronic antidepressant treatment with venlafaxine or imipramine and effects on blood pressure and heart rate: assessment by automatic 24-hour monitoring. Pharmacopsychiatry. 1996 Mar;29(2):72-8. doi: 10.1055/s-2007-979548.
Pubmed: 8741025
Thase ME: Antidepressant options: venlafaxine in perspective. J Clin Psychopharmacol. 1996 Jun;16(3 Suppl 2):10S-18S; discussion 18S-20S.
Pubmed: 8784644
Cunningham LA, Borison RL, Carman JS, Chouinard G, Crowder JE, Diamond BI, Fischer DE, Hearst E: A comparison of venlafaxine, trazodone, and placebo in major depression. J Clin Psychopharmacol. 1994 Apr;14(2):99-106.
Pubmed: 8195464
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