物质信息
ID:4573
名称和标识
商标名
Pristiq
IUPAC标准名
4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenol
IUPAC传统名
desvenlafaxine
别名
Desvenlafaxine
化合物性质
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描述信息
Drug Groups
approved
Description
Desvenlafaxine, the major active metabolite of venlafaxine, is an antidepressant from the serotonin-norepinephrine reuptake inhibitor (SNRI class). Desvenlafaxine may be used to treat major depressive disorder and is being studied for use in the management of vasomotor symptoms in postmenopausal women.
Indication
Desvenlafaxine is indicated for the treatment of major depressive disorder in adults.
Pharmacology
Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor. It lacks significant activity on muscarinic-cholinergic, H1-histaminergic, or α1-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.
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.
Affected Organisms
Humans and other mammals
Biotransformation
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.
Absorption
Absolute bioavailability is ~ 80% and is unaffected by food.
Half Life
The mean terminal half life is 11.1 hours and may be prolonged in patients with renal and/or moderate to severe hepatic impairment.
Protein Binding
~ 30%, protein binding is independent of drug concentration.
Elimination
Excreted in the urine. Approximately 45% of the total oral dose is excreted unchanged in urine. Approximately 19% of the total oral dose is excreted as the glucuronide metabolite and < 5% is excreted as the oxidative metabolite, N,O-didesmethylvenlafaxine. Excreted in human milk.
Distribution
3.4 L/kg, distribution into nonvascular compartments
References
•
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.
External Links
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参考文献
• 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
• 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
• 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
• 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
• 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
• Wyeth Laboratories Inc. Pristiq? (desvenlafaxine succinate) extended-release tablets prescribing information. Philadelphia, PA; 2010 Sept.
• 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
• 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
• 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