Methods of treating affective disorders using derivatives of (-)- venlafaxine

Abstract

Methods of preparing, and compositions comprising, derivatives of (-)-venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.

Description

1. FIELD OF INVENTION[0001] The invention relates to optically pure derivatives of (-)-venlafaxine, methods of their synthesis, compositions comprising them, and methods of their use.2. BACKGROUND OF THE INVENTION[0002] A number of nontricyclic antidepressants have recently been developed that diminish the cardiovascular and anticholinergic liability characteristic of tricyclic antidepressants. Some of these compounds are used as anti-obesity agents and have shown promise in the treatment of cerebral function disorders such as Parkinson's disease and senile dementia. See, e.g., WO 94 / 00047 and WO 94 / 00114. The nontricyclic compound venlafaxine, chemically named (.+-.)-1-[2-(dimethylamino)-1-(4-m-ethoxyphenyl)ethyl]-cyclohexanol, is an antidepressant which has been studied extensively and which is described in, for example, U.S. Pat. No. 4,761,501 and Pento, J. T. Drugs of the Future 13(9):839-840 (1988). Its hydrochloride salt is currently commercially available in the United States...

AI Technical Summary

Benefits of technology

[0008] The compounds and compositions of the invention possess potent activity for treating or preventing the above-described disorders while reducing or avoiding adverse effects including, but not limited to, sustained hypertension, headache, asthenia, sweating, nausea, constipation, somnolence, dry mouth, dizziness, insomnia, nervousness, anxiety, blurred or blurry vision, and abnormal ejaculation / orgasm or impotence in males. In particular, adverse effects associated with the administration of racemic venlafaxine are reduced or avoided by the use of optically pure derivatives of (-)-venlafaxine. Compositions of the invention can also exhibit long half lives as compared to racemic venlafaxine.

Problems solved by technology

Studies directed at understanding the activity of O-desmethylvenlafaxine as compared to its parent have been hampered, however, by the metabolic difference between laboratory animals and man in their exposure to venlafaxine.

These adverse effects can significantly limit the dose level, frequency, and duration of drug therapy.

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