Methods of treating and preventing depression using didesmethylsibutramine

Abstract

Methods are disclosed for the treatment and prevention of disorders and conditions such as, but are not limited to: eating disorders; weight gain; obesity; irritable bowel syndrome; obsessive-compulsive disorders; platelet adhesion; apnea; affective disorders such as attention deficit disorders, depression, and anxiety; male and female sexual function disorders; restless leg syndrome; osteoarthritis; substance abuse including nicotine and cocaine addiction; narcolepsy; pain such as neuropathic pain, diabetic neuropathy, and chronic pain; migraines; cerebral function disorders; chronic disorders such as premenstrual syndrome; and incontinence. Pharmaceutical compositions and dosage forms are also disclosed which comprise a racemic or optically pure sibutramine metabolite and an optional additional pharmacologically active compound.

What is claimed is:  
     
         1 . A method of treating or preventing sexual dysfunction which comprises administering to a patient in need of such treatment or prevention therapeutically or prophylactically effective amounts of a sibutramine metabolite, or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, or prodrug thereof, and a phosphodiesterase inhibitor.  
     
     
         2 . The method of  claim 1  wherein the sibutramine metabolite is optically pure.  
     
     
         3 . The method of  claim 2  wherein the sibutramine metabolite is (R)-desmethylsibutramine, (S)-desmethylsibutramine, (R)-didesmethylsibutramine, or (S)-didesmethylsibutramine.  
     
     
         4 . The method of  claim 1  wherein the phosphodiesterase inhibitor is a PDE5 or PDE6 inhibitor.  
     
     
         5 . The method of  claim 4  wherein the phosphodiesterase inhibitor is sildenophil, desmethylsildenophil, vinopocetine, milrinone, amrinone, pimobendan, cilostamide, enoximone, peroximone, vesnarinone, rolipram, R020-1724, zaprinast, dipyridamole, or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, prodrug, optically and pharmacologically active stereoisomer, or a pharmacologically active metabolite thereof.  
     
     
         6 . The method of  claim 1  wherein the amount of sibutramine metabolite administered is from about 0.1 mg to about 60 mg/day.  
     
     
         7 . The method of  claim 6  wherein the amount of sibutramine metabolite administered is from about 2 mg to about 30 mg/day.  
     
     
         8 . The method of  claim 7  wherein the amount of sibutramine metabolite administered is from about 5 mg to about 15 mg/day.  
     
     
         9 . The method of  claim 1  wherein the sibutramine metabolite and/or the phosphodiesterase inhibitor is administered transdermally or mucosally.  
     
     
         10 . The method of  claim 1  wherein the patient is male.  
     
     
         11 . The method of  claim 10  wherein the sexual dysfunction is erectile dysfunction.  
     
     
         12 . The method of  claim 1  wherein the patient is female.  
     
     
         13 . A method of treating or preventing a cerebral function disorder which comprises administering to a patient in need of such treatment or prevention therapeutically or prophylactically effective amounts of a sibutramine metabolite, or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, or prodrug thereof, and a phosphodiesterase inhibitor.  
     
     
         14 . The method of  claim 13  wherein the cerebral function disorder is senile dementia, Alzheimer's type dementia, memory loss, amnesia/amnestic syndrome, disturbance of consciousness, coma, lowering of attention, speech disorders, Parkinson's disease, Lennox syndrome, autism, epilepsy, hyperkinetic syndrome, or schizophrenia.  
     
     
         15 . The method of  claim 13  wherein the sibutramine metabolite is optically pure.  
     
     
         16 . The method of  claim 15  wherein the sibutramine metabolite is (R)-desmethylsibutramine, (S)-desmethylsibutramine, (R)-didesmethylsibutramine, or (S)-didesmethylsibutramine.  
     
     
         17 . The method of  claim 13  wherein the phosphodiesterase inhibitor is a PDE5 or PDE6 inhibitor.  
     
     
         18 . The method of  claim 17  wherein the phosphodiesterase inhibitor is sildenophil, desmethylsildenophil, vinopocetine, milrinone, amrinone, pimobendan, cilostamide, enoximone, peroximone, vesnarinone, rolipram, R020-1724, zaprinast, dipyridamole, or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, prodrug, optically and pharmacologically active stereoisomer, or a pharmacologically active metabolite thereof.  
     
     
         19 . The method of  claim 13  wherein the amount of sibutramine metabolite administered is from about 0.1 mg to about 60 mg/day.  
     
     
         20 . The method of  claim 19  wherein the amount of sibutramine metabolite administered is from about 2 mg to about 30 mg/day.  
     
     
         21 . The method of  claim 20  wherein the amount of sibutramine metabolite administered is from about 5 mg to about 15 mg/day.  
     
     
         22 . A method of treating or preventing restless leg syndrome which comprises administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of a racemic or optically pure sibutramine metabolite, or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof.  
     
     
         23 . The method of  claim 22  wherein the sibutramine metabolite is optically pure.  
     
     
         24 . The method of  claim 23  wherein the sibutramine metabolite is (R)-desmethylsibutramine, (S)-desmethylsibutramine, (R)-didesmethylsibutramine, or (S)-didesmethylsibutramine.  
     
     
         25 . The method of  claim 22  which further comprises the administration of pergolide, carbidopa, levodopa, oxycodone, carbamazepine, or gabapentin, or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, prodrug, optically and pharmacologically active stereoisomer, or pharmacologically active metabolite thereof.  
     
     
         26 . A pharmaceutical composition comprising a sibutramine metabolite, or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, or prodrug thereof, and a phosphodiesterase inhibitor.  
     
     
         27 . The pharmaceutical composition of  claim 26  wherein the sibutramine metabolite is optically pure.  
     
     
         28 . The pharmaceutical composition of  claim 27  wherein the sibutramine metabolite is (R)-desmethylsibutramine, (S)-desmethylsibutramine, (R)-didesmethylsibutramine, or (S)-didesmethylsibutramine.  
     
     
         29 . The pharmaceutical composition of  claim 28  wherein the phosphodiesterase inhibitor is sildenophil, desmethylsildenophil, vinopocetine, milrinone, amrinone, pimobendan, cilostamide, enoximone, peroximone, vesnarinone, rolipram, R020-1724, zaprinast, dipyridamole, or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, prodrug, optically and pharmacologically active stereoisomer, or a pharmacologically active metabolite thereof.  
     
     
         30 . The pharmaceutical composition of  claim 26  wherein the sibutramine metabolite is in an amount of from about 0.1 mg to about 60 mg.  
     
     
         31 . The pharmaceutical composition of  claim 30  wherein the sibutramine metabolite is in an amount of from about 2 mg to about 30 mg.  
     
     
         32 . The pharmaceutical composition of  claim 31  wherein the sibutramine metabolite is in an amount of from about 5 mg to about 15 mg.  
     
     
         33 . The pharmaceutical composition of  claim 26  wherein the phosphodiesterase inhibitor is in an amount of from about 0.5 mg to about 500 mg.  
     
     
         34 . The pharmaceutical composition of  claim 33  wherein the phosphodiesterase inhibitor is in an amount of from about 1 mg to about 350 mg.  
     
     
         35 . The pharmaceutical composition of  claim 34  wherein the phosphodiesterase inhibitor is in an amount of from about 2 mg to about 250 mg.  
     
     
         36 . The pharmaceutical composition of  claim 26  wherein the pharmaceutical composition is adapted for oral, mucosal, rectal, parenteral, transdermal, or subcutaneous administration.  
     
     
         37 . The pharmaceutical composition of  claim 36  wherein the pharmaceutical composition is adapted for oral, mucosal, or transdermal administration.  
     
     
         38 . A lactose-free pharmaceutical composition which comprises a sibutramine metabolite, or a pharmaceutically acceptable salt, solvate, or clathrate thereof, a phosphodiesterase inhibitor, and a pharmaceutically acceptable excipient.  
     
     
         39 . The pharmaceutical composition of  claim 38  wherein the excipient is croscarmellose sodium, microcrystalline cellulose, pre-gelatinized starch, or magnesium stearate.  
     
     
         40 . The pharmaceutical composition of  claim 39  wherein said pharmaceutical composition is substantially free of mono- or di-saccharides.