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 disturbance in a human who is in need of such treatment 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 R1 and R 2  are cyclized with the attached nitrogen atom to produce a 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 sexual disturbance is selected from the group consisting of hypoactive sexual desire disorder, female sexual arousal disorder, female orgasmic disorder, and male orgasmic disorder.  
     
     
         15 . The method according to  claim 14  where the sexual disturbance is hypoactive sexual desire disorder.  
     
     
         16 . The method according to  claim 14  where the sexual disturbance is female sexual arousal disorder.  
     
     
         17 . The method according to  claim 14  where the sexual disturbance is female orgasmic disorder.  
     
     
         18 . The method according to  claim 14  where the sexual disturbance is male orgasmic disorder.  
     
     
         19 . 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.  
     
     
         20 . The method according to  claim 19  where the compound of formula (A) or pharmaceutically acceptable salt is administered orally, intra-nasally, buccally, or intra-pulmonary.  
     
     
         21 . The method according to  claim 20  where the compound of formula (A) or pharmaceutically acceptable salt is administered orally.  
     
     
         22 . The method according to  claim 11  where the sexually therapeutically effective amount is from about 0.2 thru about 8 mg/person/dose.  
     
     
         23 . The method according to  claim 22  where the sexually therapeutically effective amount is from about 0.5 thru about 5 mg/person/dose.  
     
     
         24 . The method according to  claim 23  where the sexually therapeutically effective amount is from about 1 thru about 3 mg/person/dose.  
     
     
         25 . 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.  
     
     
         26 . The method according to  claim 25  where the pharmaceutically acceptable salt is (5R)-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Z)-2-butenedioate (1:1).  
     
     
         27 . 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.  
     
     
         28 . 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.  
     
     
         29 . The method according to  claim 28  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.  
     
     
         30 . The method according to  claim 29  where the compound of formula (A) or pharmaceutically acceptable salt is administered about 0.5 hr prior to sexual activity.  
     
     
         31 . The method according to  claim 11  where the human does not have Parkinson's disease.  
     
     
         32 . The method according to  claim 11  where the human does not experience postural hypotension.  
     
     
         33 . 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.  
     
     
         34 . The method according to  claim 33  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.  
     
     
         35 . The method according to  claim 34  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.  
     
     
         36 . The method according to  claim 11  where the compound of formula (A) is (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione.  
     
     
         37 . The method according to  claim 36  where the pharmaceutically acceptable salt is (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione maleate.