化合物信息

Drug Groups

approved

Description

Venlafaxine (Effexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. It is prescribed for the treatment of clinical depression and anxiety disorders. Due to the pronounced side effects and suspicions that venlafaxine may significantly increase the risk of suicide it is not recommended as a first line treatment of depression. However, it is often effective for depression not responding to SSRIs. Venlafaxine was the sixth most widely-used antidepressant based on the amount of retail prescriptions in the US (17.1 million) in 2006. [Wikipedia]

Indication

For the management of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder (social phobia), panic disorder with or without agoraphobia, and vasomotor symptoms in women with breast cancer and in postmenopausal women.

Pharmacology

Venlafaxine, an antidepressant agent structurally and pharmacologically unrelated to other antidepressants and agents used to treat generalized anxiety disorder, is used to treat melancholia, generalized anxiety disorder (GAD), panic disorder, post-traumatic stress disorder, and hot flashes in breast cancer survivors.

Toxicity

Most patients overdosing with venlafaxine develop only mild symptoms. However, severe toxicity is reported with the most common symptoms being CNS depression, serotonin toxicity, seizure, or cardiac conduction abnormalities. Venlafaxine's toxicity appears to be higher than other SSRIs, with a fatal toxic dose closer to that of the tricyclic antidepressants than the SSRIs. Doses of 900 mg or more are likely to cause moderate toxicity. Deaths have been reported following large doses.

Affected Organisms

Biotransformation

Undergoes extensive first pass metabolism in the liver to its major, active metabolite, ODV, and two minor, less active metabolites, N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine. Formation of ODV is catalyzed by cytochrome P450 (CYP) 2D6, whereas N-demethylation is catalyzed by CYP3A4, 2C19 and 2C9. ODV possesses antidepressant activity that is comparable to that of venlfaxine.

Absorption

Bioavailability is 45% following oral administration.

Half Life

5 hours

Protein Binding

venlafaxine, 27%; ODV, 30%

Elimination

Renal elimination of venlafaxine and its metabolites is the primary route of excretion.

Distribution

* 7.5 ± 3.7 L/kg [venlafaxine]
* 5.7 ± 1.8 L/kg [O-desmethylvenlafaxine(active metabolite)]

Clearance

* 1.3 +/- 0.6 L/h/kg

References

External Links