Method of treating sexual disturbances

Abstract

The present invention is a method of treating sexual disturbances in humans and inducing mating in non-human mammals using the compounds of formula (A) in a dosage range where the sexually therapeutic amount is from about 0.2 thru 8 mg/person/dose and where the sexually mating amount is from about 0.003 thru 0.2 mg/kg/dose.

1 - 10 . (Canceled).  
     
     
         11 . A method of treating a sexual deficiency state in a human who has epilepsy, craniopharyngioma, hypogonadism or who has had a hysterectomyoophorectomy, hysterectomy or oophorectomy which comprises administering a sexually therapeutically effective amount of a compound of the formula (A)  
       
         
           
           
               
               
           
         
       
       where 
 R 1 , R 2  and R 3  are the same or different and are: 
 —H,  
 C 1 -C 6  alkyl,  
 C 3 -C 5  alkenyl,  
 C 3 -C 5  alkynyl,  
 C 3 -C 5  cycloalkyl,  
 C 4 -C 10  cycloalkyl,  
 phenyl substituted C 1 -C 6  alkyl, —NR 1 R 2  where R 1  and R 2  are cyclized with the attached nitrogen atom to produce pyrrolidiyl, piperidinyl, morphoninyl, 4-methyl piperazinyl or imidazolyl;  
 
 X is: 
 —H,  
 C 1 -C 6  alkyl,  
 —F, —Cl, —Br, —I,  
 —OH,  
 C 1 -C 6  alkoxy,  
 cyano,  
 carboxamide,  
 carboxyl,  
 (C 1 -C 6  alkoxy)carbonyl,  
 
 A is: 
 CH,  
 CH 2 ,  
 CH-(halogen) where halogen is —F, —Cl, —Br, —I,  
 CHCH 3 ,  
 C═O,  
 C═S  
 C—SCH 3 ,  
 C═NH,  
 C—NH 2    
 C—NHCH 3 ,  
 C—NHCOOCH 3 ,  
 C—NHCN,  
 SO 2 ,  
 N;  
 
 B is: 
 CH 2 ,  
 CH,  
 CH-(halogen) where halogen is as defined above,  
 C═O,  
 N,  
 NH,  
 N—CH 3 ,  
 
 D is: 
 CH,  
 CH 2 ,  
 CH-(halogen) where halogen is as defined above,  
 C═O,  
 O,  
 N,  
 NH,  
 N—CH 3 ;  
 and n is 0 or 1, and where   is a single or double bond, with the provisos:  
 
 (1) that when n is 0, and 
 A is CH 2 , CH-(halogen) where halogen is as defined above, CHCH 3 , C═O, C═S, C═NH, SO 2 ;  
 
 then D is CH 2 , CH-(halogen) where halogen is as defined above, C═O, O, NH, N—CH 3 ,  
 (2) that when n is 0, and 
 A is CH, C—SCH 3 , C—NH 2 , C—NHCH 3 , C—NHCOOCH 3 , C—NHCN, N; then  
 D is CH, N;  
 
 (3) that when n is 1, and 
 A is CH 2 , CH-(halogen) where halogen is as defined above, CHCH 3 , C═O, C═S, C═NH, SO 2 ; and  
 B is CH 2 , CH-(halogen) where halogen is as defined above, C═O, NH, N—CH 3 ; then  
 D is CH 2 , C═O, O, NH, N—CH 3 ;  
 
 (4) that when n is 1, and 
 A is CH, C—SCH 3 , C—NH 2 , C—NHCH 3 , C—NHCOOCH 3 , C—NHCN, N; and  
 B is CH, N; then  
 D is CH 2 , C═O, O, NH, N—CH 3 ;  
 
 (5) that when n is 1, and 
 A is CH 2 , CHCH 3 , C═O, C═S, C═NH, SO 2 , and  
 B is CH, N; then  
 D is CH, N;  
 or a pharmaceutically acceptable salt thereof to the human.  
 
 
     
     
         12 . The method according to  claim 11  where the human is a male.  
     
     
         13 . The method according to  claim 11  where the human is a female.  
     
     
         14 . The method according to  claim 11  where the human has epilepsy.  
     
     
         15 . The method according to  claim 11  where the human has craniopharyngioma.  
     
     
         16 . The method according to  claim 11  where the human has hypogonadism.  
     
     
         17 . The method according to  claim 11  where the human has had a hysterectomyoophorectomy.  
     
     
         18 . The method according to  claim 11  where the human has had a hysterectomy.  
     
     
         19 . The method according to  claim 11  where the human has oophorectomy.  
     
     
         20 . The method according to  claim 11  where the compound of formula (A) or pharmaceutically acceptable salt is administered orally, intra-nasally, buccally, intra-pulmonary, parenterally, or rectally.  
     
     
         21 . The method according to  claim 20  where the compound of formula (A) or pharmaceutically acceptable salt is administered orally, intra-nasally, buccally, or intra-pulmonary.  
     
     
         22 . The method according to  claim 21  where the compound of formula (A) or pharmaceutically acceptable salt is administered orally.  
     
     
         23 . The method according to  claim 11  where the sexually therapeutically effective amount is from about 0.2 thru about 8 mg/person/dose.  
     
     
         24 . The method according to  claim 23  where the sexually therapeutically effective amount is from about 0.5 thru about 5 mg/person/dose.  
     
     
         25 . The method according to  claim 24  where the sexually therapeutically effective amount is from about 1 thru about 3 mg/person/dose.  
     
     
         26 . The method according to  claim 11  where the compound of formula (A) is (5R)-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one.  
     
     
         27 . The method according to  claim 26  where the pharmaceutically acceptable salt is (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Z)-2-butenedioate (1:1).  
     
     
         28 . The method according to  claim 11  where the pharmaceutically acceptable salt is selected from the group consisting of salts of the following acids: methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, CH 3 —(CH 2 ) n —COOH where n is 0 thru 4, and HOOC—(CH 2 ) n —COOH where n is as defined above.  
     
     
         29 . The method according to  claim 11  where the compound of formula (A) or pharmaceutically acceptable salt is administered from about 10 minutes to about 8 hr prior to sexual activity.  
     
     
         30 . The method according to  claim 29  where the compound of formula (A) or pharmaceutically acceptable salt is administered from about 0.5 hr to about 1 hr prior to sexual activity.  
     
     
         31 . The method according to  claim 30  where the compound of formula (A) or pharmaceutically acceptable salt is administered about 0.5 hr prior to sexual activity.  
     
     
         32 . The method according to  claim 11  where the human does not have Parkinson's disease.  
     
     
         33 . The method according to  claim 11  where the human does not experience postural hypotension.  
     
     
         34 . The method according to  claim 11  where the compound of formula (A) or pharmaceutically acceptable salt is used in combination with a sexually effective amount of one or more vascular smooth muscle relaxation agents where the compound of formula (A) or pharmaceutically acceptable salt is administered within 8 hours prior to sexual activity and the vascular smooth muscle relaxation agent is administered to the human within a sexually effective time period prior to sexual activity.  
     
     
         35 . The method according to  claim 34  where the vascular smooth muscle relaxation agent is selected from the group consisting of phosphodiesterase type 5 inhibitors, phosphodiesterase type 3 inhibitors, non-selective phosphodiesterase inhibitors, nitric oxide donor drugs, alpha type 1 adrenergic receptor antagonists, alpha type 2 adrenergic receptor antagonists, prostaglandin E1 receptor agonists (PGE1), and vasoactive intestinal polypeptide (VIP) agents.  
     
     
         36 . The method according to  claim 35  where the vascular smooth muscle relaxation agent is selected from the group consisting of sildenafil, ICOS-351, milrinone, papaverine, linsidomine, phentolamine, yohimbine, prostaglandin E1 (PGE1), and VIP.  
     
     
         37 . The method according to  claim 11  where the compound of formula (A) is (5R)-5-(methylamino)-5,6-dihydro4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione.  
     
     
         38 . The method according to  claim 37  where the pharmaceutically acceptable salt is (5R)-5-(methylamino)-5,6-dihydro4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione maleate.