Venlafaxine Hydrochloride

Dual serotonin/noradrenalin re-uptake inhibitor that displays ~ 30-fold higher affinity for SERT than NET (K_i values are 82 and 2480 nM respectively). Antidepressant; increases swimming and climbing behavior in the forced-swim test in rats.

[Possible Relation Between Antenatal Venlafaxine Use and VACTERL Association in a Newborn: A Case Report].[Pubmed:28291300]

Turk Psikiyatri Derg. 2017 Spring;28(1):67-70.

Major depressive disorder is common during antenatal period and many women are prescribed antidepressant drugs despite no antidepressant can be regarded as definitely safe in pregnancy. Previous studies have suggested links between gestational use of selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI) and certain birth defects. VACTERL association is a rare group of congenital malformations which were observed to occur together more often than would be expected by chance. Diagnosis requires coexistence of at least three congenital malformations from vertebral (V), anal (A), cardiac (C), tracheoesophageal (TE), renal (R), and limb (L) regions. Here, a case of a newborn female whose mother's gestational history revealed venlafaxine use before and during her pregnancy is reported. This newborn had anal atresia, patent ductus arteriosus, tracheoesophageal fistula, and upper limb anomalies. To the best of authors' knowledge this is the first report of VACTERL association possibly related to gestational use of SSRI or SNRI.

The influence of a single and chronic administration of venlafaxine on tramadol pharmacokinetics in a rabbit model.[Pubmed:28364695]

Pharmacol Rep. 2017 Jun;69(3):555-559.

BACKGROUND: The combined use of tramadol with selective serotonin and norepinephrine reuptake inhibitors e.g. venlafaxine may be associated with serotonin syndrome. No previous studies exist examining the influence of a weak CYP2D6 inhibitor venlafaxine on the pharmacokinetics of tramadol. Therefore, the aim of this study was to determine the effect of a single and chronic administration of venlafaxine on the pharmacokinetics of tramadol using a rabbit model. METHODS: Adult New Zealand white rabbits of both sexes (n=21) were used. Animals received 100mg of tramadol per os (one slow release tablet) and 75mg of venlafaxine (one prolonged release capsule), and were divided into four groups: control group - a single dose of tramadol alone, 1day group - a single dose of tramadol and venlafaxine, 7 and 14days groups - seven and fourteen days administration of venlafaxine once daily plus a single dose of tramadol on the last day of the study. RESULTS: Venlafaxine administration over a period of 7 and 14days resulted in faster elimination of tramadol compared to the control group: significantly higher values of k el, and lower values of t1/2kel and MRT for the 7 and 14days group were observed. Although no differences in bioavailability of tramadol were obtained. CONCLUSION: Using a rabbit model, there is no evidence that the combined administration of tramadol and venlafaxine may increase the plasma exposure of tramadol and therefore increase the risk of serotonin syndrome.

Sertraline and venlafaxine improves motor performance and neurobehavioral deficit in quinolinic acid induced Huntington's like symptoms in rats: Possible neurotransmitters modulation.[Pubmed:28178592]

Pharmacol Rep. 2017 Apr;69(2):306-313.

BACKGROUND: Huntington Disease is autosomal, fatal and progressive neurodegenerative disorder for which clinically available drugs offer only symptomatic relief. Emerging strides have indicated that antidepressants improve motor performance, restore neurotransmitters level, ameliorates striatal atrophy, increases BDNF level and may enhance neurogenesis. Therefore, we investigated sertraline and venlafaxine, clinically available drugs for depression with numerous neuroprotective properties, for their beneficial effects, if any, in quinolinic acid induced Huntington's like symptoms in rats. METHODS: Rats were administered quinolinic acid (QA) (200 nmol/2mul saline) intrastriatal bilaterally on 0day. Sertraline and venlafaxine (10 and 20mg/kg, po) each were administered for 21days once a day. Motor performance was assessed using rotarod test, grip strength test, narrow beam walk test on weekly basis. On day 22, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH and Nitrite), neuroinflammation (TNF-alpha, IL-1beta and IL-6) and neurochemical analysis (GABA, glutamate, norepinephrine, dopamine, serotonin, DOPAC, HVA and 5-HIAA). RESULTS: QA treatment significantly altered body weight, motor performance, oxidative defense (increased LPO, nitrite and decreased GSH), pro-inflammatory cytokines levels (TNF-alpha, IL-6 and IL-1beta), neurochemical level (GABA, glutamate, nor-epinephrine, dopamine, serotonin, HVA, DOPAC, 5-HIAA). Sertraline and venlafaxine at selected doses significantly attenuated QA induced alterations in striatum. CONCLUSION: The present study suggests that modulation of monoamines level, normalization of GABA and glutamatergic signaling, anti-oxidant and anti-inflammatory properties could underlie the neuroprotective effect of sertraline and venlafaxine in QA induced Huntington's like symptoms.

A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters.[Pubmed:16140280]

Biol Psychiatry. 2006 Mar 1;59(5):408-14.

BACKGROUND: Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT. Serotonergic effects occur with lower doses, whereas both serotonergic and noradrenergic effects occur with higher doses of venlafaxine. Chronic treatment of rats with selective serotonin reuptake inhibitors decreases SERT binding sites, whereas similar treatment with selective norepinephrine reuptake inhibitors decreases NET binding sites. We hypothesized that venlafaxine would affect monoamine transporters dose-dependently, with low doses causing selective reduction of SERT binding sites and higher doses reducing both SERT and NET binding sites. METHODS: Rats were treated for 21 days with a low (15 mg/kg/day) or high (70 mg/kg/day) dose of venlafaxine, vehicle, or other antidepressants. The SERT and NET density was determined by quantitative autoradiography. RESULTS: Neither dose of venlafaxine nor amitriptyline reduced binding to either the SERT or NET. In rats with noradrenergic terminals destroyed by 6-hydroxydopamine, venlafaxine still failed to reduce SERT binding. Also, rats treated simultaneously with sertraline plus desipramine exhibited reductions in both SERT and NET binding. CONCLUSIONS: Chronic venlafaxine treatment affected SERT and NET binding differently from paroxetine or desipramine. The inability of venlafaxine to reduce SERT or NET binding sites is not due to its dual uptake inhibiting properties.

The serotonin/noradrenaline reuptake inhibitor venlafaxine attenuates acquisition, but not maintenance, of intravenous self-administration of heroin in rats.[Pubmed:16325805]

Eur J Pharmacol. 2005 Dec 28;528(1-3):103-9.

Opioids and antidepressants are frequently used for the treatment of various pain conditions. A combination of both drug classes may be more effective than either treatment alone, and combined treatment with an antidepressant may result in an opiate-sparing effect. Although it has been shown that antidepressants can attenuate self-administration of psychomotor stimulant and depressant drugs, it is not known whether they also attenuate self-administration of opiates. To determine whether venlafaxine, a serotonin/noradrenaline reuptake inhibitor with antidepressive and analgesic properties, affects acquisition and maintenance of intravenous heroin self-administration in rats, male Long-Evans rats were trained to press a lever in order to receive heroin (0.05 mg/kg/infusion) under a fixed ratio or a progressive ratio schedule. A control group was trained in a fixed ratio food-reinforced operant procedure. The effect of venlafaxine on operant responding for heroin and food was assessed both during acquisition and, in separate groups of rats, during maintenance (i.e., after acquisition) of self-administration behaviour. Daily treatment with venlafaxine (10 mg/kg i.p.) before the operant session attenuated the acquisition of responding for heroin, but not for food. However, when tested during the maintenance phase in rats showing stable responding, acute treatment with venlafaxine only marginally affected operant responding for heroin under a fixed ratio:10 schedule of reinforcement, and neither acute nor subchronic (once daily during 4 weeks) venlafaxine treatment affected responding under a progressive ratio schedule. Thus, daily treatment with an antidepressant attenuates the acquisition of heroin self-administration in a behaviourally specific manner, while having only marginal effects on maintenance of heroin self-administration.