venlafaxine (Effexor)
Inhibition by venlafaxine of the increase in norepinephrine output in rat prefrontal cortex elicited by acute stress or by the anxiogenic drug FG 7142.

Dazzi L, Vignone V, Seu E, Ladu S, Vacca G, Biggio G.

Department of Experimental Biology B. Loddo, University of Cagliari, Italy. dazzi unica.it

Venlafaxine is an antidepressant drug that inhibits the reuptake of serotonin and norepinephrine with different efficacies. The effects of repeated administration of this drug on the increase in the extracellular concentration of norepinephrine in the prefrontal cortex, induced by stress or by the anxiogenic drug FG 7142, were studied in freely moving rats. Exposure to foot-shock stress induced a marked increase (+120%) in the extracellular norepinephrine concentration in the prefrontal cortex of control rats. Long-term administration of venlafaxine (10 mg/kg i.p., once a day for 21 days) reduced the effect of stress on norepinephrine output by 75%. This effect of venlafaxine persisted for at least 5 days after discontinuation of drug treatment. Acute administration of FG 7142 (20 mg/kg i.p.), a benzodiazepine receptor inverse agonist, increased norepinephrine output (+90%) in control rats. Chronic treatment with venlafaxine prevented the effect of FG 7142. In contrast, the acute administration of this antidepressant had no effect on the stress- or FG 7142-induced increase in norepinephrine output. These plastic changes in the sensitivity of norepinephrine neurones to foot-shock stress and to an anxiogenic drug may reveal an important neuronal mechanism for the physiological regulation of emotional state. Furthermore, this mechanism might be relevant to the anxiolytic and antidepressant effects of venlafaxine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12095070&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Acute and continuation treatment adequacy with venlafaxine extended release compared with fluoxetine.

Yu-Isenberg KS, Fontes CL, Wan GJ, Geissler EC, Harada AS.

Pharmacoeconomics and Health Outcomes Research Department, Prescription Solutions, Costa Mesa, California 92626, USA. yu.isenberg sbcglobal.net

STUDY OBJECTIVE: To compare treatment adequacy in the management of depression during the acute and continuation phases between patients newly treated with venlafaxine extended release (XR) and those newly treated with fluoxetine. DESIGN: Retrospective observational analysis of pharmacy claims data. SETTING: Large California-based managed care organization. PATIENTS: A total of 11,298 patients newly prescribed venlafaxine XR or fluoxetine between January 1, 2000, and February 28, 2001, and continuously enrolled throughout the study, as well as a subset of 7430 patients who continued taking venlafaxine XR or fluoxetine during the follow-up period. MEASUREMENTS AND MAIN RESULTS: The Health Plan Employer Data and Information Set definition was used for continuous antidepressant treatment during the acute and continuation phases. Treatment adequacy was determined for those deemed continuous. Patients receiving within +/- 10% of the target dose for each drug (venlafaxine XR 75-150 mg, fluoxetine 20 mg) were defined as receiving an adequate dose. Logistic regression was used to evaluate venlafaxine XR versus fluoxetine on treatment adequacy, controlling for age, sex, physician specialty, and pharmacy benefit. The unadjusted adequacy rate for the venlafaxine XR-only group was 79% versus 57% for the fluoxetine-only group for 84 continuous days (p<0.0001) and 77% versus 52%, respectively, for 180 continuous days (p<0.0001). The adjusted odds ratios of achieving treatment adequacy with venlafaxine XR only versus that with fluoxetine only were 3.05 (95% confidence interval [CI] 2.65-3.52) for 84 continuous days and 3.57 (95% CI 3.00-4.24) for 180 continuous days. CONCLUSION: Patients newly prescribed venlafaxine XR were at least 3 times more likely to achieve treatment adequacy for 84 and 180 days compared with those newly prescribed fluoxetine. Treatment adequacy as a proxy for optimal treatment may be an important factor to consider when selecting an antidepressant drug.

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Effexor, Effexor XR

venlafaxine (Effexor)
[An improved novel method of venlafaxine synthesis]

[Article in Chinese]

Sheng R, Liu T, Hu YZ.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, China.

OBJECTIVE: To synthesize venlafaxine with an improved novel method. METHODS: p-methoxypheny lethyl-acid was reacted with SOCl(2) to produce acyl chloride which was reacted with N,N-dimethylamine solution to get amide; then through Ivanov reaction and reduction by KBH(4)/BF(3).Et(2)O to yield venlafaxine. RESULT: Venlafaxine was successfully synthesized by using this method with an yield rate of 50.3%. CONCLUSION: The improved method is suitable for industrial production of venlafaxine.

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Effexor, Effexor XR

venlafaxine (Effexor)
Mechanisms for the inhibition of genital vascular responses by antidepressants in a female rabbit model.

Angulo J, Cuevas P, Cuevas B, Gupta S, Saenz de Tejada I.

Fundacion para la Investigacion y el Desarrollo en Andrologia, Madrid, Spain.

Vaginal and clitoral vasodilator responses (genital vascular responses; GVRs) to pelvic nerve electrical stimulation in female rabbits were measured by laser Doppler flow needle probes. The intravenous administration of various treatments was evaluated. GVRs were attenuated by a nitric-oxide synthase inhibitor (48.5 and 51.8% of control at 8 Hz in the vagina and clitoris, respectively) and norepinephrine (NE) (78.5 and 61.5%), whereas serotonin (5-HT) had no inhibitory effect. The selective 5-HT reuptake inhibitor (SSRI) escitalopram did not modify GVRs, whereas the SSRI paroxetine dose-dependently inhibited GVRs in female rabbits (43.3 and 53.1% at 5 mg/kg). GVRs were also significantly inhibited by the 5-HT and NE reuptake inhibitors venlafaxine (53.4 and 52.6% at 5 mg/kg) and duloxetine (40.9 and 37.4% at 1 mg/kg). L-arginine prevented the inhibitory effects of paroxetine (105.5 and 115.3%) and partially prevented duloxetine-induced reduction of GVRs but had no effect on the inhibition of GVRs induced by venlafaxine. Conversely, the alpha-adrenergic receptor blocker phentolamine had no effect on paroxetine-induced reduction of GVRs, partially prevented the inhibitory effects of duloxetine, and fully prevented the effects of venlafaxine (93.0 and 96.7%). Duloxetine-induced inhibition of GVRs was completely prevented by combined administration of L-arginine and phentolamine (123.5 and 103.6%). Although 5-HT or the highly selective SRI escitalopram did not inhibit GVRs, NE or inhibition of nitric oxide (NO) synthesis did. Inhibition of the NO pathway by paroxetine and duloxetine or activation of alpha-adrenergic mechanisms by venlafaxine and duloxetine lead to antidepressant-induced inhibition of GVRs in female rabbits.

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Effexor, Effexor XR

venlafaxine (Effexor)
[Venlafaxine extended release for the treatment of chronic pain. A series of 50 cases]

[Article in Spanish]

Galvez R, Caballero J, Atero M, Ruiz S, Romero J.

Unidad de Dolor, Servicio de Anstesia, Hospital Universitario Virgen de las Nieves, Granada. rgalvez fundacionhvn.org

INTRODUCTION: The objective of this study is to investigate analgesic effectiveness and safety of venlafaxine extended release in chronic pain of any etiology. METHODS: Six month, observational, open study, carried out in two pain units. Initially, a daily dose of 75 mg of venlafaxine extended release was administered, increasing it to 150 mg, following clinical criteria. Treatment response was measured using the Visual Analogue Scale (VAS), rest and mobilization, Hospital Anxiety and Depression Scale (HAD) and Eastern Cooperative Oncology Group (ECOG) and an adverse event sheet to record adverse events occurring during the study. RESULTS: The study was carried out in a 50 patient sample with a mean age of 57.1 +/- 1.8 years, with chronic pain. A total of 85-90 % of the patients was maintained with a daily dose of 75 mg of venlafaxine extended release. This produced a gradual reduction of the VAS scores at rest (significant reduction of 5.2 +/- 1.1 to 2.7 +/- 1.5 points; (p<0.0005) and mobilization (significant reduction of 5.5 +/- 0.8 to 3.1 +- 1.6 points; p<0.0005). Pain relief increased progressively. Regarding physical activity measured by the ECOG scale, there was a reduction of the percentage of patients and increase of outpatients. Tolerability to venlafaxine was "excellent", "very good" or "good" for 72% of the patients. CONCLUSIONS: Extended release venlafaxine can be an effective and well-tolerated treatment in patients with chronic pain of any etiology, although it must be investigated in depth.

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Effexor, Effexor XR