Desvenlafaxine succinate monohydrate

Nalivela, Venu; Sreekanth, B.; Thaimattam, Ram; Devarakonda, Surya

doi:10.1107/s0108270108010019

Cited by 11 publications

(17 citation statements)

References 8 publications

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“…In vitro functional assays indicate that DVS is approximately 10-fold more potent as an inhibitor of 5-HT uptake than NE uptake. [22][23][24] Affi nity for muscarinic, cholinergic, histamine H 1 −, and alpha 1 adrenergic receptors is very low. 22,23 DVS increases extracellular levels of both NE and 5-HT without increasing DA levels in the hypothalamus of ovariectomized rats.…”

Section: Pharmacodynamics and Pharmacokineticsmentioning

confidence: 99%

Desvenlafaxine in the treatment of major depressive disorder

Lourenço

Kennedy²

2009

NDT

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Major depressive disorder (MDD) is among the most incapacitating conditions in the world. The emergence of the selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) antidepressants has improved the treatment of MDD. Desvenlafaxine succinate (DVS) is the succinate salt of the isolated major active metabolite of venlafaxine, O-desmethylvenlafaxine: it is the third SNRI to become available in the United States, and was approved in 2008 by the US Food and Drug Administration (FDA) for the treatment of MDD. Early investigations showed therapeutic effi cacy for doses between 50 and 400 mg/day; however in doses above 100 mg/day there were incremental increases in side effects. Nausea was the most frequent adverse effect. Hence the recommended dosing for DVS is in the 50 to 100 mg range. Desvenlafaxine is excreted in urine, it is minimally metabolized via the CYP450 pathway, and is a weak inhibitor of CYP2D6. A reduced risk for pharmacokinetic drug interactions is a potential advantage over other SNRI. Further head-to-head trials involving comparisons of DVS in the 50 to 100 mg dose range with currently available SSRI and SNRI antidepressants are required. Evidence for relapse prevention is available in the 200 to 400 mg dose range, but this needs to be demonstrated in the 50 to 100 mg dose range, as well as health economic measures and quality of life evaluations.

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Section: Pharmacodynamics and Pharmacokineticsmentioning

confidence: 99%

Desvenlafaxine in the treatment of major depressive disorder

Lourenço

Kennedy²

2009

NDT

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“…SNRI antidepressants increase levels of these neurotransmitters variably [64]. Venlafaxine and desvenlafaxine preferentially antagonize 5-HT transporter proteins at all doses and NE transporter proteins at higher doses [35]–[37], [64], suggesting that the high desvenlafaxine dose used in the current study may have rapidly increased hippocampal neurogenesis through dual effects on 5-HT and NE levels not achieved by the lower dose. In addition, desvenlafaxine exhibits a slightly higher affinity for the 5-HT transporter protein and a much higher affinity for the NE protein and therefore, could have produced its effects at the higher dose through a NE-linked mechanism not activated by the same dose of venlafaxine.…”

Section: Discussionmentioning

confidence: 72%

“…Venlafaxine is converted in the liver to its active metabolite O -desmethylvenlafaxine (the free base of desvenlafaxine succinate) by the cytochrome P450 enzyme CYP2D6 [34]. Both venlafaxine and desvenlafaxine succinate are now marketed as SNRI antidepressants that competitively bind serotonin (5-HT) transporters with relatively similar affinities (Ki = 82 nM and 40.2 nM, respectively) and at higher doses norepinephrine (NE) transporters with variable affinities (Ki = 2480 nM and 558.4 nM, respectively), possibly with weak dopamine (DA) transporter binding [35]–[37]. Theoretically these SNRIs should produce similar effects but the pharmacokinetic properties of desvenlafaxine and some clinical data suggest that desvenlafaxine may produce a faster response onset [38]–[40].…”

Section: Introductionmentioning

confidence: 99%

Desvenlafaxine May Accelerate Neuronal Maturation in the Dentate Gyri of Adult Male Rats

et al. 2014

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Adult hippocampal neurogenesis has been linked to the effects of anti-depressant drugs on behavior in rodent models of depression. To explore this link further, we tested whether the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine impacted adult hippocampal neurogenesis differently than its primary active SNRI metabolite desvenlafaxine. Adult male Long Evans rats (n = 5–6 per group) were fed vehicle, venlafaxine (0.5 or 5 mg) or desvenlafaxine (0.5 or 5 mg) twice daily for 16 days. Beginning the third day of drug treatment, the rats were given a daily bromodeoxyuridine (BrdU; 50 mg/kg) injection for 5 days to label dividing cells and then perfused 2 weeks after the first BrdU injection to confirm total new hippocampal cell numbers and their phenotypes. The high desvenlafaxine dose increased total new BrdU+ cell number and appeared to accelerate neuronal maturation because fewer BrdU+ cells expressed maturing neuronal phenotypes and more expressed mature neuronal phenotypes in the dentate gyri of these versus vehicle-treated rats. While net neurogenesis was not increased in the dentate gyri of rats treated with the high desvenlafaxine dose, significantly more mature neurons were detected. Our data expand the body of literature showing that antidepressants impact adult neurogenesis by stimulating NPC proliferation and perhaps the survival of neuronal progeny and by showing that a high dose of the SNRI antidepressant desvenlafaxine, but neither a high nor low venlafaxine dose, may also accelerate neuronal maturation in the adult rat hippocampus. These data support the hypothesis that hippocampal neurogenesis may indeed serve as a biomarker of depression and the effects of antidepressant treatment, and may be informative for developing novel fast-acting antidepressant strategies.

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“…Desvenlafaxine is asynthetic formofthe major active metabolite of venlafaxine and is being investigated as the first non-hormonal based treatment for menopause. It is aracemic mixture and is reported to exist in four crystalline polymorphs [2].Furthermore the crystal structure of venlafaxine hydrochloride [3], am onoclinic polymorph of venlafaxine hydrochloride [4],venlafaxine itself [5], desvenlafaxine succinate monohydrate [6] and two polytypes of desvenlafaxine succinate monohydrate [7]h aveb eenr eported. Thec rystal structure of at ernary complex,4 -(2-pyridyl)pyridinium-3,5-dinitrobenzoate-3,5-dinitrobenzoic acid (1/1/1), is apparent in the literature [8], and an orthorhombic-to-monoclinic temperature-dependent phase transition of hexa-methylenetetraminium-3,5-dinitrobenzoate-3,5-dinitrobenzoic acid monohydrate in the solid state has been described [9].…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of desvenlafaxinium 3,5-dinitrobenzoate 3,5-dinitrobenzoic acid monohydrate, C30H35N5O15

Kaur

Yathirajan

Byrappa

et al. 2014

Zeitschrift Für Kristallographie - New Crystal Structures

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Source of materialDesvenlafaxine succinatewas obtained as agift sample from R. L. Fine Chem,B engaluru,I ndia. As olution of desvenlafaxine succinate in water was treated with ammonium hydroxide solution till apH>7was reached upon which awhite precipitate of desvenlafaxine was obtained. The precipitate was filtered and driedinopen airovernight.Itwas used for the preparation of the dinitrobenzoate salt without further purification. Desvenlafaxine (200 mg, 0.76 mmol) and 3,5-dinitrobenzoic acid (161 mg,0.76 mmol) were dissolved in hot methanol and stirred at 333 Kfor 30 minutes. The resulting solution was allowed to cool slowly to room temperature. The salt obtained was filtered and dried in a vacuum desiccator over phosphorous pentoxide. The resulting compound was recrystallized from acetonitrile by slow evaporation. Experimental detailsCarbon-bound Hatomswere placed in calculated positions (C-H 0.95 Å, C-H 0.99 Åfor methylene groups and C-H 1.00 Åfor methine groups) and were included in the refinement in the riding model approximation, with U iso (H) setto1.2U eq (C). The Hatoms of the methyl groups were allowed to rotate with afixed angle around the C-C bond to best fit the experimental electron density (HFIX 137 [7]h aveb eenr eported. Thec rystal structure of at ernary complex,4 -(2-pyridyl)pyridinium-3,5-dinitrobenzoate-3,5-dinitrobenzoic acid (1/1/1), is apparent in the literature [8], and an orthorhombic-to-monoclinic temperature-dependent phase transition of hexa-methylenetetraminium-3,5-dinitrobenzoate-3,5-dinitrobenzoic acid monohydrate in the solid state has been described [9]. In the crystal, amolecule of water is present next to onea dditional molecule of the -n on-dissociated -c arboxylic acid. While the least-squares planes defined by the atomsofthe nitro groups of the deprotonated carboxylic acid enclose angles of 5.8(2)°and 9.8(2)°with the plane defined by the carbon atomsof thearomaticsystemtheyare bonded to,t he least-squares plane defined by theatoms of thecarboxylate groupintersectwiththe aromat's planeatanangle of 13.88(14)°.T he respective values fort he co-crystallized carboxylic acid are found at 4.9(2)°and 7.25(16)°for thenitro groups and 11.12(16)°for the least-squares plane defined by the non-hydrogen atomsofthe carboxylic acid group on the one hand and the plane defined by the carbon atoms of the aromatic system they are bonded to on the other hand. According to apuckering analysis, the saturated six-membered ring adopts a 4 C 1 conformation ( C24 C C21 ) [10,11]. In the crystal, hydrogen bonds of the N-H×××Oaswell as the O-H×××Otype areob-

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Desvenlafaxine succinate monohydrate

Cited by 11 publications

References 8 publications

Desvenlafaxine in the treatment of major depressive disorder

Desvenlafaxine in the treatment of major depressive disorder

Desvenlafaxine May Accelerate Neuronal Maturation in the Dentate Gyri of Adult Male Rats

Crystal structure of desvenlafaxinium 3,5-dinitrobenzoate 3,5-dinitrobenzoic acid monohydrate, C30H35N5O15

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