4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenol

• ChemBase ID: 4438
• Molecular Formular: C16H25NO2
• Molecular Mass: 263.3752
• Monoisotopic Mass: 263.18852905
• SMILES: C(C(c1ccc(cc1)O)C1(CCCCC1)O)N(C)C
• Canonical SMILES: CN(CC(C1(O)CCCCC1)c1ccc(cc1)O)C
• InChI: InChI=1S/C16H25NO2/c1-17(2)12-15(13-6-8-14(18)9-7-13)16(19)10-4-3-5-11-16/h6-9,15,18-19H,3-5,10-12H2,1-2H3
• InChIKey: KYYIDSXMWOZKMP-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenol
• IUPAC Traditional name: desvenlafaxine
• Brand Name: Pristiq
• Synonyms: Desvenlafaxine; 4-(2-(Dimethylamino)-1-(1-hydroxycyclohexyl)-ethyl)phenol; 4-[2-(Dimethylamino)-1-(1-hydroxycyclo-hexyl)ethyl]phenol; DVS 233; Desvenlafaxine; O-Desmethylvenlafaxine; Pristiq; WY 45233; D,L-O-Desmethyl Venlafaxine; 4-(2-(Dimethylamino)-1-(1-hydroxycyclohexyl)ethyl)phenol

Database IDs

• CAS Number: 93413-62-8
• MDL Number: MFCD00871934
• PubChem SID: 160967870; 99443254
• PubChem CID: 125017

CALCULATED PROPERTIES

JChem

• Acid pKa: 10.111714
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): -0.5600763
• LogD (pH = 7.4): 1.0721254
• Log P: 2.2934265
• Molar Refractivity: 78.5419 cm^3
• Polarizability: 30.689209 Å^3
• Polar Surface Area: 43.7 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.6
• LOG S: -2.27
• Solubility (Water): 1.40e+00 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; Methanol (Sparingly)
• Apperance: White to Off-White Solid
• Melting Point: 208-213°C

Safety Information

• Storage Condition: -20°C Freezer
• Storage Warning: IRRITANT
• TSCA Listed: false

Pharmacology Properties

• Target: 5-HT Receptor

Product Information

• Purity: 95+%
• Salt Data: Free Base

DETAILS

DrugBank - DB06700

• 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: Wikipedia; RxList; PDRhealth; Drugs.com

Toronto Research Chemicals - D296500

A metabolite of Venlafaxine (V120000), a selective serotonin noradrenaline reuptake inhibitor (SNRI). Used as an antidepressant.

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.
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• Huq, F., et al.: J. Pharmacol. Toxicol., 3, 27 (2006)
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