venlafaxine (Effexor)
Venlafaxine: new preparation. Just another antidepressant.

[No authors listed]

(1) Venlafaxine is a non tricyclic, non MAOI antidepressant which has been assessed mainly in placebo-controlled trials. Some of the available trials against other antidepressants are methodologically unsound. (2) Placebo-controlled trials have established the antidepressant efficacy of venlafaxine at a dose of 75-375 mg/day in ambulatory patients, and 350 mg/day in inpatients. (3) Two trials against fluoxetine and three against imipramine showed no difference in efficacy. (4) The adverse effect profile of venlafaxine is similar to that of serotonin reuptake inhibitors. At high doses (over 200 mg/day), venlafaxine can provoke arterial hypertension. Amphetamine-like behavioural effects cannot be ruled out.

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Effexor, Effexor XR

venlafaxine (Effexor)
Postnatal development of rats exposed to fluoxetine or venlafaxine during the third week of pregnancy.

da-Silva VA, Altenburg SP, Malheiros LR, Thomaz TG, Lindsey CJ.

Departamento de Fisiologia, Universidade Federal Fluminense, Niteroi, RJ, Brasil. mflvilm vm.uff.br

The aim of the present study was to compare the toxic effects of fluoxetine (F) (8 and 16 mg/kg) and venlafaxine (V) (40 and 80 mg/kg) administered during the third week of pregnancy on early development of rats. Both antidepressants were administered by gavage on pregnancy days 15 to 20 to groups of 10 to 12 animals each. Duration of gestation, food and water consumtion, number of live pups and birth weight were recorded. Litters were culled to six pups at birth (day 1) and followed for growth until weaning (day 25). On day 60, a male and a female from each litter were injected with the 5-HT1 agonist, 5-methoxy-N,N-dimethyltryptamine (6 mg/kg, i.p.) and the serotonergic syndrome was graded. Fluoxetine but not venlafaxine reduced the duration of pregnancy when compared to the control (C) group (F = 21.1 days and C = 21.6 days, mean, P < 0.02: maximum = 22 days and minimum = 21 days in both groups). The highest doses of both fluoxetine, 16 mg/kg (F16), and venlafaxine, 80 mg/kg (V80), reduced the food intake of pregnant rats, resulting in different rates of body weight gain during treatment (from pregnancy day 15 to day 20): F16 = 29.0 g, V80 = 28.7 g vs C = 39.5 g (median). Birth weight was influenced by treatment and sex (P < 0.05; two-way ANOVA). Both doses of fluoxetine or venlafaxine reduced the body weight of litters; however, the body weight of litters from treated dams was equal to the weight of control litters by the time of weaning. At weaning there was no significant difference in weight between sexes. There was no difference among groups in number of live pups at birth, stillbirths, mortality during the lactation period or in the manifestation of serotonergic syndrome in adult rats. The occurrence of low birth weight among pups born to dams which did not show reduced food ingestion or reduction of body weight gain during treatment with lower doses of fluoxetine or venlafaxine suggests that these drugs may have a deleterious effect on prenatal development when administered during pregnancy. In addition, fluoxetine slightly but significantly affected the duration of pregnancy (about half a day), an effect not observed in the venlafaxine treated groups.

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Effexor, Effexor XR

venlafaxine (Effexor)
Altered open-field behavior in experimental chronic hepatic encephalopathy after single venlafaxine and citalopram challenges.

Apelqvist G, Wikell C, Hindfelt B, Bergqvist PB, Andersson G, Bengtsson F.

Institute of Laboratory Medicine, Department of Clinical Pharmacology, Lund University Hospital, Sweden.

RATIONALE: Latent or manifest chronic hepatic encephalopathy (HE) symptomatology often includes affective symptoms. It is therefore warranted to investigate the functional outcome of novel antidepressants when chronic HE prevails. OBJECTIVE: Portacaval shunt (PCS) in rats is a widely used experimental model for chronic HE, a neuropsychiatric syndrome accompanying liver dysfunction. HE is believed to arise from a primary alteration in neurotransmission in the CNS. PCS has been reported to increase the metabolism of serotonin in the brain, and thus the central serotonin nerve of PCS rats may contain more serotonin than normal. However, the functional relevance of this serotonergic alteration in terms of affecting behavioral performance of PCS rats has been only rarely studied. METHODS: Locomotor and rearing activities were recorded in PCS and sham-operated control rats. A single subcutaneous challenge with saline versus either the mixed serotonin/noradrenaline reuptake inhibitor venlafaxine (10 mg x kg(-1)) or the selective serotonin reuptake inhibitor citalopram (5 mg x kg(-1)) were performed. RESULTS: The PCS-saline injected rats showed reduced locomotor and rearing activity compared with sham-saline treated rats. While no significant differences could be observed following the venlafaxine challenge to controls, the PCS-venlafaxine challenged rats displayed reduced behavioral activity as compared to PCS-saline treated rats. The PCS-citalopram rats, however, displayed increased activity compared with the PCS-saline rats while, again, no effect of the citalopram challenge to controls was found. CONCLUSIONS: The present study show altered but opposite behavior in PCS rats, when challenged with either venlafaxine or citalopram, compared to PCS control rats. These findings therefore support the contention that caution should be advocated when CNS monoamine active drugs are used in liver-impaired subjects until better delineation of the combined pharmacodynamic and pharmacokinetic outcome for each such drug in this condition has been made.

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Effexor, Effexor XR

venlafaxine (Effexor)
Electrochemical behaviour of Venlafaxine and its determination in pharmaceutical products using square wave voltammetry.

Lima JL, Loo DV, Delerue-Matos C, da Silva AS.

CEQUP/Departamento de Quimica-Fisica, Faculdade de Farmacia da Universidade do Porto, Portugal.

An electrochemical method for the determination of Venlafaxine in pharmaceutical formulations recently available on the European market is described. The electrochemical oxidation of Venlafaxine was studied at a HMDE electrode over a wide pH range (1.9-10.0) of buffered aqueous solutions using different potential sweep techniques. The results obtained showed that the best definition of the analytical signals was found in boric acid/potassium tetrahydroxoborate buffer at pH 8.7 using anodic stripping square wave voltammetry. Recovery trials were performed to assess the accuracy of results and these were compared to those provided by a HPLC technique according to the method described in literature and to the features of the pharmaceutical formulations. A relative deviation of < 0.2% was obtained. With the developed methodology, the limit of detection was 0.124 mg/l.

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Effexor, Effexor XR

venlafaxine (Effexor)
Venlafaxine: acute and chronic effects on 5-hydroxytryptamine levels in rat brain in vivo.

Gur E, Dremencov E, Lerer B, Newman ME.

Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Venlafaxine is a dual serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline uptake inhibitor which has been claimed to have an onset of antidepressant action which is faster than for other comparable drugs. The effects of venlafaxine on brain 5-HT levels in vivo have not yet been examined. Acute administration of venlafaxine to rats by i.p. injection resulted in dose-dependent increases in cortical and hippocampal 5-HT levels, as measured by in vivo microdialysis, over the range 5-20 mg/kg. The effect of venlafaxine (10 mg/kg i.p.) was potentiated by prior administration of pindolol (10 mg/kg s.c.) in hippocampus but not in frontal cortex. Daily administration of venlafaxine (5 mg/kg i.p.) for 4 weeks did not change basal 5-HT levels in either brain area. The effect of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.2 mg/kg s.c.) to reduce 5-HT levels was unaffected by chronic venlafaxine at this dose, indicating that there was no change in sensitivity of presynaptic 5-HT1A autoreceptors.

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Effexor, Effexor XR