Antidepressants venlafaxine

A critical review by Olver et al. (2001) on so-called third-generation antidepressants (venlafaxine, reboxetine, nefazodone, mirtazapine) covered 30 controlled therapeutic trials and a number of relapse prevention studies. Questions addressed were overall efficacy, speed of onset and safety but, according to this review, none of the third-generation antidepressants was specifically tested with respect to its potential effects on cognitive function in depressed patients. 

Muth EA, Moyer JA, Haskins JT, et al. Husbands GEM. Biochemical, neurophysiological, and behavioral effects of Wy-45,233 and other identified metabolites of the antidepressant venlafaxine. Drug Dev Res 1991 23 191-199. 

FIGURE 8—10. In the late 1990s the antidepressants venlafaxine XR and others have become first-line treatments for generalized anxiety disorder. Thus, antidepressants are now first-line treatments for both depression and anxiety disorders, rendering the classification of antidepressant versus anxiolytic inappropriate for many antidepressants. 

Sedative antidepressants (venlafaxine, trazodone, nefazodone, TCAs, mianserin, mirtazepine). 

Vollmar P, Nessler S, Kalluri SR, Hartung HP, Hemmer B (2008) The antidepressant venlafaxine ameliorates murine experimental autoimmune encephalomyelitis by suppression of pro-inflammatory cytokines. IntJ. Neuropsychopharmacol . - 2. 

Along with this emphasis on particular disorders, recent pharmaceutical industry literature for conditions like depression and psychosis refers increasingly commonly to imbalances in brain chemicals, echoing the statements of official psychiatric literature described in Chapter 1. On depression, Eli Lilly s website claims that a growing amount of evidence supports the view that people with depression have an imbalance of the brain s neurotransmitters. .. many scientists believe that an imbalance in serotonin may be an important factor in the development and severity of depression (Eli Lilly 2006a, accessed 10.02.2006). Wyeth, makers of the antidepressant Venlafaxine (brand name Effexor... 

Horst WD, Preskorn SH. Mechanisms of action and clinical characteristics of three atypical antidepressants venlafaxine, nefazodone, bupropion. Journal of Affective Disorders 1998 51 237-254. 

Drugs used in the treatment of depression and psychosis can alter the metabolism of terfenadine. When the antidepressant venlafaxine was given to steady state (37.5 mg bd for 3 days and then 75 mg bd for 5 days), the pharmacokinetics of a single dose of terfenadine 120 mg were not altered and there were no changes in the electrocardiogram (13). The authors concluded that cardiotoxicity is unlikely to arise with co-administration of terfenadine and venlafaxine. 

Shams ME, Arneth B, Hieinke C, et al. CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. J Clin Pharm Ther 2006 31(5) 493-502. 

This unique reactivity of /V-mcthyl C-H bonds was exploited in a short total synthesis of the antidepressant venlafaxine (140, Scheme 32) [104], In the key event, substrate 137 was treated with aryldiazoacetate 138 and Rli2(.S -IX)SP)4, providing product 139 in 62% yield and 93% ee. Dimethylation of the amine followed by addition of a bis-Grignard to the ester afforded the HC1 salt of (S)-venlafaxine. 

But breast cancer survivors tend to have lots of hot flashes, about thirty-five per week, says Maki. The sudden depletion of hormones blindsides your internal thermostat. Skin flushes, sweating, perhaps even palpitations, nausea and dizziness, are the body s valiant attempt to regulate itself. They are terrible and persistent, affecting sleep and quality of life, she says. If a healthy woman without breast cancer takes estrogen, it basically cures her of hot flashes. But a woman undergoing treatment for breast cancer does not have a choice in terms of therapy because she can t take estrogen. Some patients find the antidepressant venlafaxine helpful." ... 

Troy SM, Rudolph R, Mayersohn M, Chiang ST. The influence of cimetidine on the disposi-tic kinetics of the antidepressant venlafaxine. J Clin Pharmacol (1998) 38, 467-74. 

H. Yang, S.T. Lopina, Extended release of a novel antidepressant, venlafaxine, based on anionic polyamidoamine dendrimers and poly(ethylene glycol) containing semi-interpenetrating networks, J. Biomed. Mater. Res. A 72 (2005) 107-114. 

Scheme 1.16 Application of the C—H bond functionalization in the asymmetric synthesis of antidepressant venlafaxine reported by Davies.

A subsequent study from the Davies group illustrated the synthetic utility of this Rh"-catalyzed intermolecular C—H bond insertion approach by the asymmetric synthesis of antidepressant venlafaxine (Scheme 1.16). ... 

The antidepressant venlafaxine and its metabolite oxydesmethylvenlafaxine were extracted from plasma and separated on a C g/cyanopropyl mixed mode column (electrochemical detector at 0.65 V and 0.98 V). These compounds have UV chromophores as well (phenyl groups). A 10-min analysis was achieved with a 30/70 water (50mM KH2PO4 at pH 4.8)/methanol mobile phase. Note that the buffer has a very low capacity here (nearly equidistant from the first two phosphate pK values). A standard range from 0 to 200 ng/mL was developed and detection limits of 0.5 ng/mL (S/N = 3) were reported [566]. 

Show how the antidepressant venlafaxine (Effexor) can be synthesized from these readily available starting materials. Is venlafaxine chiral If so, how many of the possible stereoisomers are formed in this synthesis ... 

Problem 20.27 What Grignard reagent and carbonyl compound can be used to prepare the antidepressant venlafaxine (trade name Effexor) ... 

Figure 7.27 Dealkylation on O and S is also a common metabolic pathway which operates by the same mechanism as W-dealkylation. Top an example of 0-demethylation is seen with the antidepressant venlafaxine. Bottom the anesthetic methitural provides...

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