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Product Details:

  • CAS No: 93413-62-8
  • AHFC code: 28:16.04.16
  • Synonyms: Desvenlafaxine, O-desmethylvenlafaxine, ODV, Pristiq
  • ATC Code: N06AX23
  • Chemical Formula: C10H20N2S4
  • Molecular Weight: 263.3752
  • Assay/Purity: Typically NLT 98%
  • DrugBank: DB06700
  • SMILES: CN(C)CC(C1=CC=C(O)C=C1)C1(O)CCCCC1
  • InChl: KYYIDSXMWOZKMP-UHFFFAOYSA-N
  • PubChem: 125017
  • IUPAC: 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenol

Additional Details

Indication:
Desvenlafaxine is indicated for the treatment of major depressive disorder in adults.
Pharmacodynamics:
Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor. It lacks significant activity on muscarinic-cholinergic, H1-histaminergic, or _1-adrenergic receptors in vitro. Desvenlafaxine does not appear to exert activity against calcium, chloride, potassium and sodium ion channels and also lacks monoamine oxidase (MAO) inhibitory activity. It was also shown to lack significant activity again the cardiac potassium channel, hERG, in vitro. Compared to other SNRIs, desvenlafaxine undergoes simple metabolism, has a low risk of drug-drug interactions and does not have to be extensively titrated to reach a therapeutic dose. Some of the limitations of desvenlafaxine include moderate efficacy in the treatment of major depressive disorder, similar safety and tolerability profile to other SNRIs and possible transient discontinuation symptoms upon cessation of therapy.
Mode of Action:
Desvenlafaxine, the major active metabolite of venlafaxine, is a selective serotonin and norepinephrine reuptake inhibitor. The clinical effect of desvenlafaxine is thought to occur via potentiation of serotonin and norepinephrine in the central nervous system. Unlike venlafaxine, desvenlafaxine is thought to have a differential serotonergic and noradrenergic activity profile.
Metabolism:
The primary route of metabolism is via conjugation mediated by UGT isoforms. Desvenlafaxine also undergoes oxidative N-demethylation via cytochrome P450 3A4 to a minor extent.
Toxicity:
The safety and tolerability of desvenlafaxine is similar to other SNRIs. Common side effects upon initiation or dose increase include increased blood pressure and heart rate, agitation, tremor, sweating, nausea, headache, and sleep disturbances. May cause sexual dysfunction and weight loss in some patients. May cause increases in fasting serum total cholesterol, LDL cholesterol, and triglycerides. Withdrawal effects may occur and thus, the dose of desvenlafaxine should be titrated down prior to discontinuation.
General Reference:
Ilett KF, Watt F, Hackett LP, Kohan R, Teoh S: Assessment of Infant Dose Through Milk in a Lactating Woman Taking Amisulpride and Desvenlafaxine for Treatment-Resistant Depression. Ther Drug Monit. 2010 Oct 5. Pubmed Kamath J, Handratta V: Desvenlafaxine succinate for major depressive disorder: a critical review of the evidence. Expert Rev Neurother. 2008 Dec;8(12):1787-97. Pubmed Kornstein SG, Jiang Q, Reddy S, Musgnung JJ, Guico-Pabia CJ: Short-term efficacy and safety of desvenlafaxine in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder. J Clin Psychiatry. 2010 Aug;71(8):1088-96. Pubmed Liebowitz MR, Tourian KA: Efficacy, Safety, and Tolerability of Desvenlafaxine 50 mg/d for the Treatment of Major Depressive Disorder:A Systematic Review of Clinical Trials. Prim Care Companion J Clin Psychiatry. 2010;12(3). pii: PCC.09r00845. Pubmed Mason JN, Deecher DC, Richmond RL, Stack G, Mahaney PE, Trybulski E, Winneker RC, Blakely RD: Desvenlafaxine succinate identifies novel antagonist binding determinants in the human norepinephrine transporter. J Pharmacol Exp Ther. 2007 Nov;323(2):720-9. Epub 2007 Aug 2. Pubmed Montgomery SA, Fava M, Padmanabhan SK, Guico-Pabia CJ, Tourian KA: Discontinuation symptoms and taper/poststudy-emergent adverse events with desvenlafaxine treatment for major depressive disorder. Int Clin Psychopharmacol. 2009 Nov;24(6):296-305. Pubmed Oganesian A, Shilling AD, Young-Sciame R, Tran J, Watanyar A, Azam F, Kao J, Leung L: Desvenlafaxine and venlafaxine exert minimal in vitro inhibition of human cytochrome p450 and p-glycoprotein activities. Psychopharmacol Bull. 2009;42(2):47-63. Pubmed Pae CU, Park MH, Marks DM, Han C, Patkar AA, Masand PS: Desvenlafaxine, a serotonin-norepinephrine uptake inhibitor for major depressive disorder, neuropathic pain and the vasomotor symptoms associated with menopause. Curr Opin Investig Drugs. 2009 Jan;10(1):75-90. Pubmed Reddy S, Kane C, Pitrosky B, Musgnung J, Ninan PT, Guico-Pabia CJ: Clinical utility of desvenlafaxine 50 mg/d for treating MDD: a review of two randomized placebo-controlled trials for the practicing physician. Curr Med Res Opin. 2010 Jan;26(1):139-50. Pubmed Wyeth Laboratories Inc. Pristiq (desvenlafaxine succinate) extended-release tablets prescribing information. Philadelphia, PA; 2010 Sept.
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