venlafaxine (Effexor)
Rapid determination of venlafaxine and O-desmethylvenlafaxine in human plasma by high-performance liquid chromatography with fluorimetric detection.

Vu RL, Helmeste D, Albers L, Reist C.

VA Medical Center, Long Beach, CA 90822, USA.

A rapid and sensitive high-performance liquid chromatographic technique for simultaneous measurement of plasma venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) is described. The process begins with the extraction of VEN and ODV, with maprotiline (MAP) as internal standard, from human plasma into an intermediate organic mixture of hexane-isoamyl alcohol and finally into an aqueous solution of 0.05% phosphoric acid. Isocratic separation of VEN, ODV and MAP is carried out by utilizing a reversed-phase butyl-bonded column (C4/E) with mobile phase consisting of acetonitrile and 40 mM phosphate buffer, pH 6.8 (50:50, v/v). Detection of VEN, ODV and MAP is done by mean of fluorimetry with excitation and emission wavelengths set at 276 and 598 nm, respectively. As low as 1.0 ng/ml VEN is detectable; while the limit of detection for ODV is 5 ng/ml. C.V. (%) of intra-day samples for both VEN and ODV are less than 10% at three concentrations tested (10.0, 50.0, 100.0 ng/ml). Similarly, over the same nominal concentrations, the precision of inter-day (5 days) samples also results in C.V. (%) smaller than 10% for both compounds, except for ODV measured at 10 ng/ml (C.V.<15%). Approximately, 100% VEN can be extracted from plasma; whereas, for ODV the recovery rate is nearly 70%. This present method is rapid, sensitive, accurate and simple for routine clinical monitoring of plasma VEN and its major metabolite ODV.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9448076&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers.

Salin-Pascual RJ, Galicia-Polo L, Drucker-Colin R.

Servicio de Investigacion del Hospital Psiquiatrico Fray Bernardino Alvarez, Departamento de Fisiologia, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico City.

BACKGROUND: The purpose was to examine the effect of the antidepressant drug venlafaxine on sleep architecture and periodic leg movements of sleep (PLMS) in normal volunteers. METHOD: Eight normal volunteers were studied under laboratory sleep conditions as follows: 1 acclimatization night, 1 baseline night, and 4 consecutive nights of venlafaxine p.o. administration (75 mg during the first 2 nights and 150 mg the last 2 nights). RESULTS: Venlafaxine increased both wake time and sleep stage I. Sleep stages II and III were reduced. REM sleep time was reduced after the first venlafaxine dose, and, by the fourth night, REM sleep was completely suppressed in all volunteers. Six of the eight volunteers showed PLMS at a frequency above 25 per hour. CONCLUSION: Venlafaxine produces several sleep disturbances, which include abnormal leg movements.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9515972&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Simultaneous measurement of venlafaxine and its major metabolite, oxydesmethylvenlafaxine, in human plasma by high-performance liquid chromatography with coulometric detection and utilisation of solid-phase extraction.

Clement EM, Odontiadis J, Franklin M.

University of Oxford, Department of Psychiatry, Warneford Hospital, UK.

Venlafaxine, oxydesmethylvenlafaxine and an internal standard (paroxetine) were extracted from plasma by a solid-phase extraction technique. Chromatography was performed using isocratic reversed-phase high-performance liquid chromatography (HPLC) with coulometric endpoint detection. The standard curves were linear over the range 0-200 ng/ml for both venlafaxine and oxydesmethylvenlafaxine in plasma. The mean inter- and intra-assay coefficients of variation over the range of the standard curves were less than 10%. The absolute recovery averaged 74% for venlafaxine and 67% for oxydesmethylvenlafaxine. The sensitivity was 0.5 ng for both the analytes. Plasma profiles of the analytes following oral administration of venlafaxine, are presented.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9521568&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
An open clinical trial of venlafaxine treatment of fibromyalgia.

Dwight MM, Arnold LM, O'Brien H, Metzger R, Morris-Park E, Keck PE Jr.

Department of Psychiatry, University of Cincinnati, Ohio, USA.

Of 15 patients with fibromyalgia who were first evaluated for the presence of Axis I psychiatric diagnoses by use of the Structured Clinical Interview for DSM-IV, 11 completed an open 8-week trial with the novel antidepressant venlafaxine. Six (55%) of 11 completers experienced a > or = 50% reduction of fibromyalgia symptoms. The presence of lifetime psychiatric disorders, particularly depressive and anxiety disorders, predicted a positive response to venlafaxine. These findings suggest that it is important to assess for comorbid psychiatric disorders in patients with fibromyalgia and that venlafaxine may be helpful to some of these patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9538670&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the rat forced swimming test.

Reneric JP, Lucki I.

Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-2648, USA.

Because of clinical interest in the effects of antidepressant drugs that exert their effects on multiple neurotransmitter systems, the behavioral effects produced by combined treatment with an SSRI (fluoxetine) with a selective norepinephrine (NE; desipramine) or dopamine (DA) reuptake inhibitor (buproprion) were examined in the forced swimming test (FST), a behavioral test in rodents that predicts the clinical activity of antidepressants. Three additional compounds with mixed activity as NE-5-HT reuptake inhibitors, milnacipran, duloxetine and venlafaxine, were also examined. Desipramine and fluoxetine both reduced immobility in the FST, but desipramine increased only climbing behavior, whereas fluoxetine increased only swimming behavior. The combination of fluoxetine with desipramine or bupropion increased both climbing and swimming behaviors at certain doses, but higher doses of desipramine when combined with fluoxetine replaced swimming behavior with climbing behavior. The mixed NE-5-HT reuptake inhibitors milnacipran and duloxetine reduced immobility and increased climbing behavior, but did not alter swimming. Venlafaxine reduced immobility and increased swimming behavior, except at the highest dose tested (80 mg/kg), which increased both swimming and climbing behaviors. Thus, combining certain doses of pharmacologically selective monoamine reuptake inhibitors, or the mixed reuptake inhibitor venlafaxine, produced a pattern of mixed active behaviors in the FST (climbing and swimming) that may reflect the activity of multiple neurotransmitters, especially the combination of enhanced 5-HT and DA activity. The combination of higher doses of desipramine with fluoxetine, or compounds with mixed activity at inhibiting NE and 5-HT reuptake, demonstrated effects similar to those of desipramine alone and may reflect inhibition of the expression of serotonergic antidepressant behavioral effects by selective NE reuptake inhibitors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9551776&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR