Therapeutic Uses of Compounds Having Combined SERT, 5-HT3 and 5-HT1A Activity

Abstract

New pharmaceutical uses of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof are provided.

1 . A method of treating a disease selected from circadian rhythm disorder; difficulties in falling asleep; nocturnal arousals; early morning awakenings; sleep-disordered breathing; hypopnea syndrome; severe depression; dysthymic disorder; cyclothymia; exhaustive depression; atypical depression; mood disorder associated with a generalised medical disorder; substance induced mood disorder; recurrent depression; single episode depression; paediatric depression; post-stroke depression; peri-, pre- or post-menupausal dysphoric disorder; seasonal affective disorder (SAD); aggression and agitation in dementia or Alzheimer's disease; compulsive and attention spectrum disorders in ADHD, autism or Asperger's syndrome; leucariosis; small vessel disease; depression associated with abuse, irritability, hostility, sleep disorders, fatigue, Huntington's disease, multiple sclerosis, anxiety (anxious depression), pain, pain in the gastrointestinal tract or irritable bowl syndrome (IBS); general anxiety disorder associated with pain; impulse control disease; intermittent explosive disorder; kleptomania; pyromania; pathological gambling; trichotillomania; negative symptoms of schizophrenia; mild cognitive impairment; vascular dementia; cognitive impairment associated with Down's syndrome, tph gene mutations, ADHD, epilepsy, traumatic brain injury or Asperger's syndrome; aggression and agitation in dementia and Alzheimer's disease; chronic fatigue syndrome; stress related disorder; acute stress; stress; burn-out; insulin resistance associated with HPA-axis hyperactivity; obesity; binge eating; anorexia; bulimia nervosa; conduct disorder; behavioural disturbances; behavioural disturbances associated with dementia; behavioural disturbances in the elderly; fear of flying; fear of elevators; fear of small rooms; amblyopia; anorgasmia; delayed ejaculation; erectile dysfunction; decreased libido; abnormal orgasm; loss of libido; or decreased orgasmic sensation, the method comprising administering to a patient in need thereof a therapeutically effective amount of compound I, which is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine and pharmaceutically acceptable salts thereof, to a patient in need thereof. 
     
     
         2 . The method according to  claim 1 , wherein said patient is administered the hydrobromic acid salt of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine. 
     
     
         3 . The method according to  claim 2 , wherein said salt is crystalline. 
     
     
         4 . The method according to  claim 3 , wherein said salt is characterised by having major XRDP peaks at 6.89, 9.73, 13.78 and 14.62 (°2θ), all ±0.1 (°2θ). 
     
     
         5 . The method according to  claim 4 , wherein said salt is characterised by an XRDP as depicted in  FIG. 3 . 
     
     
         6 . The method according to  claim 1 , wherein compound I is administered to the patient in unit doses of about 1-50 mg. 
     
     
         7 . The method according to  claim 6 , wherein the patient is administered between about 1 and 20 mg per day of the hydrobromic acid salt of 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine orally. 
     
     
         8 . The method according to  claim 1 , wherein said patient is administered a therapeutically effective amount of compound I provided it is not the free base of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine in a non-crystalline form. 
     
     
         9 . The method according to  claim 1 , wherein said patient has previously received medication (or is still receiving it) for the treatment of said disease which medication was ceased or reduced (or has to be ceased or reduced) due to sleep or sexually related adverse events. 
     
     
         10 - 27 . (canceled) 
     
     
         28 . A method for the treatment of a disease selected from depression, anxiety, abuse or chronic pain comprising the administration of a therapeutically effective amount of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof to a patient in need thereof, wherein said patient has previously received medication (or is still receiving it) for the treatment of said disease which medication was ceased or reduced (or has to be ceased or reduced) due to sleep or sexually related adverse events. 
     
     
         29 - 30 . (canceled)