Piperidin-2, 6-dione pamoate salts and their use for the treatment of affective disorders

Abstract

Novel pamoate salts of certain 3-phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-diones and pharmacologically acceptable solvates thereof are devoid of the weight loss and hepatocyte changes in the rat which limited to marginally effective levels the permitted clinical doses of the corresponding hydrochlorides in the treatment or prophylaxis of stress-related affective disorders such as anxiety, depression, migraine and sleep apnoea. The preferred pamoate salts are 3(3,5-dimethoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione pamoate and, especially, 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione pamoate.

1 . A pamoate salt of a 3-phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-dione of Formula I: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  represents methoxy, ethoxy or hydroxy; 
         R 2  represents methoxy, ethoxy, hydroxy or hydrogen; and 
         n represents 2 or 3, 
       
       or a pharmacologically acceptable solvate thereof. 
     
     
         2 . A pamoate salt as claimed in  claim 1 , wherein R 1  represents methoxy and R 2  represents methoxy or hydrogen. 
     
     
         3 - 6 . (canceled) 
     
     
         7 . A pharmaceutical composition comprising a pamoate salt of a 3-phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-dione of Formula I: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  represents methoxy, ethoxy or hydroxy; 
         R 2  represents methoxy, ethoxy, hydroxy or hydrogen; and 
         n represents 2 or 3, 
       
       or a pharmacologically acceptable solvate thereof 
       and a pharmacologically acceptable diluent or carrier. 
     
     
         8 . A pharmaceutical composition as claimed in  claim 7  for the treatment or prophylaxis of a stress-related affective disorder. 
     
     
         9 - 24 . (canceled) 
     
     
         25 . A method for the treatment or prophylaxis of a stress-related affective disorder which comprises administering to a human or animal patient an effective amount of a pamoate salt of a 3-phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-dione of Formula I: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  represents methoxy, ethoxy or hydroxy; 
         R 2  represents methoxy, ethoxy, hydroxy or hydrogen; and 
         n represents 2 or 3, 
       
       or a pharmacologically acceptable solvate thereof. 
     
     
         26 . A method as claimed in  claim 25 , wherein the stress-related affective disorder is selected from the group consisting of agoraphobia; anorexia nervosa; anxiety; anxiogenisis associated with drawal from drugs of abuse; bulimia nervosa; chronic paroxysmal hemicrania; depression (including prevention of depressive recurrences); diminution of the immune response associated with anxiety, depression or bereavement; disorders of sleep initiation or maintenance; disorders of the sleep-awake schedule; dream anxiety attacks; Huntington's chorea; Kleine-Levin syndrome; memory disturbance; Meniere's disease, menstrual-associated sleep syndrome; migraine; motion sickness; nausea incompletely relieved by 5HT 3  antagonist administration, neurogenic pain; neuropathic pain; obsessive-compulsive disorder; panic attacks; posttraumatic stress disorder; pre-menstrual dysphoric disorder; recurrent brief depression; Restless Leg syndrome, schizophrenia; senile dementia; serotonin-irritation syndrome; sleep apnoea; sleep related cardiovascular symptoms; sleep related epileptic seizures; sleep-related cluster headaches; sleep-related myoclomus syndrome; social phobia; sudden infant death syndrome; and tinnitus. 
     
     
         27 . A method as claimed in  claim 26 , wherein the stress-related affective disorder is anxiety. 
     
     
         28 . A method as claimed in  claim 26 , wherein the stress-related affective disorder is depression. 
     
     
         29 . A method as claimed in  claim 26 , wherein the stress-related affective disorder is migraine. 
     
     
         30 . A method as claimed in  claim 26 , wherein the stress-related affective disorder is sleep apnoea. 
     
     
         31 - 33 . (canceled)