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PubMed2000

Antidepressant efficacy of venlafaxine.

Venlafaxine is a unique antidepressant medication with well documented efficacy and safety in the acute treatment of major depressive disorder. Reports suggest that it may also be effective in the treatment of dysthymic disorder and bipolar II depression, but the available data for these conditions are more limited compared to major depressive disorder. Several studies suggest that there may be a more rapid onset of action for venlafaxine in the treatment of major depression compared to other antidepressant pharmacotherapies, but this has not been fully established. Venlafaxine is also effective in the important long term continuation and maintenance phases of the treatment of depression.

Antidepressive Agents, Second-Generation↗
PubMed2000

Efficacy of venlafaxine in the treatment of severe depression.

Although the efficacy of available antidepressants has been well established in the treatment of mild to moderate depression, clinical research literature on severe depression is more limited, due to lack of a standardized definition for the condition and the resulting inconsistent data. Given the heterogeneous nature of severe depression, reports suggesting noradrenergic as well as serotonergic system involvement in depressive disorders, and the substantive capability of both clomipramine and TCA-SSRI combination to treat severe depression, investigation of dual-action antidepressant agent efficacy in the treatment of severe depression is warranted. The merit of one such combined-action agent, venlafaxine, is reviewed. Efficacy findings from the limited number of comparative clinical trials conducted in the severely depressed patient population suggest that, while venlafaxine has been evaluated in a broad range of depressed patients, this compound may be particularly effective for the severely ill. Pharmacological features of venlafaxine, which may benefit the patient with severe depression, include the possibility of a rapid onset of action and a dose-response curve. Based upon studies comparing venlafaxine with both placebo and other first-line antidepressants, it is concluded that venlafaxine is safe, tolerable, and effective for the treatment of severe depression.

Antidepressive Agents, Tricyclic↗
PubMed2000

Venlafaxine and treatment-resistant depression.

Treatment-resistant depression (TRD) is an important clinical problem. This paper briefly reviews the definition of TRD and summarizes methodological issues that pertain to treatment research. Recent studies of venlafaxine treatment for TRD also are reviewed. It is concluded that venlafaxine at higher doses is a reasonably well-tolerated and an effective alternative for patients with TRD and typically should be used before tricyclic antidepressants or monoamine oxidase inhibitors. Further research is needed to confirm the prediction that switching a SSRI nonresponder to venlafaxine is a more effective strategy than switching to a second SSRI. The relative merits of switching from a SSRI to venlafaxine versus adding a norepinephrine reuptake inhibitor also warrant careful study.

Cyclohexanols↗
PubMed2000

Efficacy of venlafaxine in geriatric depression.

Geriatric patients with major depression present clinical challenges not encountered in younger individuals, including a greater incidence of medical comorbidity, higher rates of multiple medication use, changes in drug metabolism due to age or physical illness, and increased sensitivity to antidepressant side effects. Nevertheless, successful treatment of depressive disorders in the elderly improves mental and physical functioning, decreases morbidity and perhaps mortality, and enhances quality of life. Recent research indicates that newer antidepressants are effective for late life depression and safer for older individuals. Among newer antidepressants, venlafaxine has a pharmacological profile that makes it an attractive choice for geriatric patients. It has limited potential to interact with other medications because it only weakly inhibits the cytochrome P450 system and binds to plasma proteins at a low level. Dosing may have to be adjusted for patients with renal failure, but typically not for those with liver disease or other medical conditions. Data from three double-blind and four open clinical trials support the safety and efficacy of venlafaxine for geriatric depression. Patients may experience transient, generally tolerable side effects such as insomnia, nausea, agitation, or dry mouth early in treatment, but more serious problems such as falls or cardiac rhythm disturbances seem to be rare. Treatment emergent hypertension occurs in a small percentage of older patients, generally at doses above 150 mg/day. Finally, emerging data suggest that venlafaxine may be effective for conditions such as stroke, anxiety, and neuropathic pain that frequently accompany depressive disorders in the elderly.

Aged↗
PubMed2000

Efficacy, safety, and tolerability of venlafaxine XR in generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a common and chronic disorder with a low rate of spontaneous remission. A complication in treatment selection is the high rates of co-morbid major depressive disorder in this population. A number of treatments exist to treat GAD. The most recent medication to gain an indication for GAD is venlafaxine XR, a serotonin/norepinephrine reuptake inhibitor that is also approved for the treatment of major depressive disorder. More than 2,000 patients with GAD have been studied in outpatient trials of venlafaxine XR with demonstrated efficacy, tolerability and safety of this compound. This article reviews these studies, both short term and longer (6 month) continuation trials. The response to venlafaxine XR in this population, combined with good tolerability, makes this agent an appropriate first-line medication for GAD. In general, treatment with antidepressants, though associated with a longer onset of action than benzodiazepines, does not produce physiological dependency, and is useful in a patient population with a high prevalence of mood disorders.

Anxiety Disorders↗
PubMed2000

Use of venlafaxine in children and adolescents: a review of current literature.

Pediatric psychopharmacology is hindered by the relative lack of controlled, empirical clinical trials [Shatzberg and Nemeroff, 1998: Washington, D.C.: The American Psychiatric Press, Inc. p 301-306]. Psychiatric disorders in children and adolescents carry considerable morbidity, impede development, and carry a significant mortality by suicide. Therefore, there is a need for studies of antidepressants and other psychotropics in children and adolescents. This article reviews the preliminary evidence that venlafaxine (Effexor), a novel antidepressant, may be useful in children and adolescents with a variety of psychiatric disorders.

Adolescent↗
PubMed2000

Use of venlafaxine in other psychiatric disorders.

Venlafaxine is a medication available by prescription in the U.S. both in an immediate release and an extended release formulation. Preclinical studies indicate it has the effect of potently blocking the serotonin and norepinephrine transporters. Venlafaxine is approved by the FDA for the treatment of major depressive disorder and generalized anxiety disorder. Suggestive evidence, mostly from open label case series, indicates efficacy of venlafaxine in several other conditions including panic disorder, social anxiety disorder, obsessive compulsive disorder, trichotillomania, ADHD, chronic pain, and fibromyalgia. The limited evidence supporting efficacy in these conditions is reviewed. Additional randomized clinical trials with placebo controls are indicated.

Anxiety↗
PubMed2001

Asymmetric induction of conduritols via AAA reactions: synthesis of the aminocyclohexitol of hygromycin A.

Two synthetic routes towards the construction of the aminocyclohexitol moiety of hygromycin A have been developed based on palladium-catalyzed asymmetric alkylation of conduritol derivatives. A protocol has been established whereby this biologically relevant molecule is formed from benzoquinone. A conduritol A derivative is synthesized in eight steps from benzoquinone and is then subjected to the palladium reaction. From this flexible intermediate, four epimers of the aminocyclitol, including the natural one, can be obtained with complete stereoselectivity. Racemic conduritol B derivatives are available in four steps from benzoquinone, and these are then made enantiomerically pure by a palladium-catalyzed dynamic kinetic resolution. From the chiral conduritol B, the aminocyclitol is available in six steps. Excellent levels of enantio- and diastereoselectivity highlight these strategies.

Alkylation↗
PubMed2001

AAA in KAT/DYKAT processes: first- and second-generation asymmetric syntheses of (+)- and (-)-cyclophellitol.

Kinetic resolutions and kinetic asymmetric transformations (KAT) as well as dynamic kinetic resolutions and dynamic kinetic asymmetric transformations (DYKAT) are important synthetic protocols. The feasibility of KAT and DYKAT processes for asymmetric allylic alkylations (AAA) is explored utilizing a single substrate--conduritol B tetraesters. Both processes can be performed resulting in excellent enantioselectivity. The impact of nucleophile and leaving group on the effectiveness of each is outlined. The ability to differentiate the various hydroxyl groups is also described. For this purpose, 4-tert-butyldimethylsiloxy-2,2-dimethylbutyric acid was developed as a nucleophile. The utility of effecting KAT/DYKAT processes through the Pd-catalyzed AAA reaction is demonstrated by efficient syntheses of both enantiomers of the potent glycosidase inhibitor cyclophellitol.

Agaricales↗
PubMed2002

Antifungal activities of selected aromatic plants growing wild in Greece.

Essential oils of Origanum onites, Satureja thymbra, Salvia fruticosa (Greek sage), and Salvia pomifera subsp. calycina plants growing wild in Greece and their components carvacrol, camphor, and 1,8-cineole, were assayed for antifungal activity against 13 fungal species. Among the fungi tested were food poisoning, plant, animals and human pathogenic species. The oils presented various degrees of inhibition against all the fungi investigated. The highest and broadest activity was shown by the carvacrol content oils (O. onites and S. thymbra), while the oil of sage was the least effective. Carvacrol exhibited the highest and 1,8-cineole the lowest level of antifungal activity among the components tested.

Antifungal Agents↗
PubMed2001

Nonaqueous capillary electrophoresis-mass spectrometry for separation of venlafaxine and its phase I metabolites.

Aqueous and nonaqueous capillary electrophoresis (NACE) were investigated for separation of venlafaxine, a new second-generation antidepressant, and its three phase I metabolites. Working at basic pH, around the venlafaxine pKa value, was effective in resolving the investigated drugs, but created considerable peak tailing. To overcome electrostatic interactions between analytes and silanol groups, investigations were also carried out at acidic pH. However, despite the addition of up to 50% v/v of organic solvents (e.g., methanol or acetonitrile), complete separation of the studied compounds was not possible. NACE was found to be an appropriate alternative to resolve venlafaxine and its metabolites simultaneously. Using a conventional capillary (fused-silica, 64.5 cm length, 50 microm inner diameter), and a methanol-acetonitrile mixture (20/80 v/v) containing 25 mM ammonium formate and 1 M formic acid, complete resolution of these closely related compounds was performed in less than 3.5 min. Selectivity, efficiency and separation time were greatly affected by the organic solvent composition. As the electric current generated in nonaqueous medium was very low, the electric field was further increased by reducing the capillary length. This allowed a baseline resolution of venlafaxine and its three metabolities in 0.7 min. Selectivity was compared in aqueous and nonaqueous media in relation to the acid-base properties of the analytes as well as to the solvation degree. Finally, the method successfully coupled on-line to mass spectrometry with electrospray ionization interface allowed significant sensitivity enhancement.

Antidepressive Agents, Second-Generation↗
PubMed2001

Use of vancomycin silica stationary phase in packed capillary electrochromatography I. Enantiomer separation of basic compounds.

Chiral separation of basic compounds was achieved by using 75 or 100 microm ID fused-silica capillaries packed with a vanoomycin-modified diol silica stationary phase. The capillary was firstly packed for about 12 cm with a slurry mixture composed of diolsilica (3:1) then with the vancomycin modified diol-silica (3:1) (23 cm), and finally with diol-silica (3:1) for about 2 cm. Frits were prepared by a heating wire at the two ends of the capillary; the detector window was prepared at 8.5 cm from the end of the capillary where vancomycin was not present. The influence of the mobile phase composition (pH and concentration, organic modifier type and concentration) on the velocity of the electroosmotic flow, chiral resolution and enantioselectivity was studied. Good enantiomeric resolution was achieved for atenolol, oxprenolol, propranolol, and venlafaxine using a mobile phase composition of 100 mM ammonium acetate solution (pH 6)/water/acetonitrile (5:5:90 v/v/v) while for terbutaline a mixture of 5:15:80 v/v/v provided the best separations. The use of methanol instead of acetonitrile caused a general increase of enantiomer resolution of the studied compounds together with a reduction of efficiency and detector response. However, the combination of acetonitrile and methanol in the mobile phase (as, e.g., 10% methanol and 80% acetonitrile) allowed to improve the enantiomer resolution with satisfactory detector response.

Acetates↗
PubMed2001

On-line capillary electrophoresis-electrospray mass spectrometry for the stereoselective analysis of drugs and metabolites.

The on-line combination of partial-filling capillary electrophoresis and electrospray ionization mass spectrometry was demonstrated for the enantioseparation of pharmaceutical drugs and metabolites, namely amphetamines, methadone, venlafaxine and selected tropane alkaloids. The partial-filling technique proved to be a suitable and efficient approach to avoid mass spectrometry (MS) source contamination, as well as signal suppression due to nonvolatile additives. To achieve chiral separation, various chiral selectors were applied, including neutral and particularly negatively charged cyclodextrins. Because of the countercurrent contribution, charged cyclodextrins were found more suitable for the on-line MS detection of separated enantiomers. Hyphenation of capillary electrophoresis (CE) with mass spectrometry was found appropriate for the stereoselective analysis of methadone in real serum samples. Moreover, the use of MS in the selected ion monitoring mode resulted in a very high selectivity, as well as improved sensitivity compared to UV detection. Finally, with atropine as a model compound, the quantitative performances of the method were evaluated and showed high sensitivity, as well as good repeatability in terms of migration time and peak area ratio.

Amphetamines↗