O-desmethylvenlafaxine and methods of preparing and using the same

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.

1 . A pharmaceutical composition which comprises (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, or clathrate thereof, and a pharmaceutically acceptable carrier or excipient.  
     
     
         2 - 3 . (canceled)  
     
     
         4 . The pharmaceutical composition of  claim 1  adapted for intravenous infusion, transdermal delivery, or oral delivery.  
     
     
         5 - 10 . (canceled)  
     
     
         11 . A pharmaceutical dosage form which comprises a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, or clathrate thereof and a pharmaceutically acceptable carrier or excipient.  
     
     
         12 . The dosage form of  claim 11  wherein said dosage form is a tablet or a capsule.  
     
     
         13 . The dosage form of  claim 11  adapted for intravenous infusion, transdermal delivery, or oral delivery.  
     
     
         14 . The dosage form of  claim 11 , wherein the therapeutically effective amount is from about 10 mg to about 1000 mg.  
     
     
         15 . The dosage form of  claim 14  wherein the therapeutically effective amount is from about 50 mg to about 500 mg.  
     
     
         16 . The dosage form of  claim 15  wherein the therapeutically effective amount is from about 75 mg to about 350 mg.  
     
     
         17 - 20 . (canceled)  
     
     
         21 . A method of preparing (±)-O-desmethylvenlafaxine which comprises contacting (O)-venlafaxine with lithium diphenylphosphide for a time and at a temperature sufficient to form (±)-O-desmethylvenlafaxine.  
     
     
         22 . Substantially pure (±)-O-desmethylvenlafaxine or a pharmaceutically acceptable salts, solvates, or clathrates thereof.  
     
     
         23 - 26 . (canceled)  
     
     
         27 . A method of treating an affective disorder in a human which comprises administering to a human in need of such treatment a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, or clathrate thereof.  
     
     
         28 . The method of  claim 27  in which said amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof, is sufficient to alleviate the affective disorder but insufficient to cause adverse effects associated with the administration of racemic venlafaxine.  
     
     
         29 . The method of  claim 27  wherein the affective disorder is depression, attention deficit disorder, or attention deficit disorder with hyperactivity.  
     
     
         30 . A method for treating obesity or weight gain in a human which comprises administering to a human in need of a reduction or maintenance in weight, a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof.  
     
     
         31 . The method of  claim 30  wherein said amount is sufficient to alleviate obesity or weight gain but insufficient to cause the adverse effects associated with administration of racemic venlafaxine.  
     
     
         32 . A method of treating disorders ameliorated by inhibition of neuronal monoamine reuptake in a human which comprises administering to a human in need of such treatment a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof.  
     
     
         33 . The method of  claim 31  in which said amount is sufficient to alleviate said disorders but insufficient to cause adverse effects associated with administration of racemic venlafaxine.  
     
     
         34 . The method of  claim 32  wherein said monoamine is dopamine.  
     
     
         35 . The method of  claim 32  wherein said disorder is Parkinson's disease or epilepsy.  
     
     
         36 . A method for treating cerebral function disorders in humans which comprises administering to a human in need of such treatment a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof.  
     
     
         37 . The method of  claim 35  wherein said amount is sufficient to alleviate cerebral function disorders but insufficient to cause adverse effects associated with administration of racemic venlafaxine.  
     
     
         38 . The method of  claim 35  wherein said disorder is caused by a cerebrovascular disease.  
     
     
         39 . The method of  claim 38  wherein said cerebrovascular disease is cerebral infarction, cerebral bleeding, cerebral arteriosclerosis, cerebral venous thrombosis and or head injuries.  
     
     
         40 . The method of  claim 35  wherein said cerebral function disorder senile dementia, Alzheimer's type dementia, memory loss or amnesia/amnestic syndrome.  
     
     
         41 . A method for treating pain in humans which comprises administering to a human in need of such treatment a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt thereof, solvate or clathrate thereof.  
     
     
         42 . The method of  claim 41  wherein said amount is sufficient to alleviate pain but insufficient to cause adverse effects associated with administration of racemic venlafaxine.  
     
     
         43 . The method of  claim 41  wherein the pain is chronic pain.  
     
     
         44 . A method of treating an obsessive-compulsive disorder in a human, which comprises administering to a human in need of such treatment a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof.  
     
     
         45 . A method of treating substance abuse in a human, which comprises administering to a human in need of such treatment a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof.  
     
     
         46 . A method of treating or preventing pre-menstrual syndrome in a human, which comprises administering to a human in need of such treatment or prevention a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof.  
     
     
         47 . A method of treating anxiety in a human which comprises administering to a human in need of such treatment a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof.  
     
     
         48 . A method of treating an eating disorder in a human which comprises administering to a human in need of such treatment a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof.  
     
     
         49 . A method of treating or preventing migraine, or migraine headaches, in a human which comprises administering to a human in need of such treatment a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof.  
     
     
         50 . A method for treating or preventing incontinence in a human which comprises administering to a human in need of such treatment a therapeutically effective amount of (±)-O-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate or clathrate thereof.  
     
     
         51 . The method of  claim 50  wherein said incontinence fecal incontinence, overflow incontinence, passive incontinence, reflex incontinence, stress urinary incontinence, urge incontinence, urinary exertional incontinence, or incontinence of urine.  
     
     
         52 - 53 . (canceled)  
     
     
         54 . The method of  claim 27  wherein (±)-O-desmethylvenlafaxine is administered by intravenous infusion, transdermal delivery, or orally as a tablet or a capsule.  
     
     
         55 . The method of  claim 27  wherein the amount of (±)-O-desmethylvenlafaxine administered is from about 10 mg to about 1000 mg per day.  
     
     
         56 . The method of  claim 55  wherein the amount administered is from about 50 mg to about 500 mg per day.  
     
     
         57 . The method of  claim 56  wherein the amount administered is from about 75 mg to about 350 mg per day.  
     
     
         58 - 59 . (canceled)