Method for the normalization of sexual response and amelioration of long term genital tissue degradation

Abstract

The present invention provides, in one embodiment, a method of normalizing the timing of sexual response in a mammal comprising the administration of an amount of a central nervous system sexual response initiator in an amount sufficient to produce genital vasodilation but less than the amount required to produce effective vasocongestive arousal. The method is applicable not only to adjusting or normalizing the timing of sexual response in humans, but in the breeding of valuable commercial animals such as horses, cattle, sheep, swine and the like and domesticated pets such as dogs and cats. In an alternative embodiment, the present invention provides a method for the prophylactic treatment of long-term tissue degradation in the genital organs comprising the administration to a mammal of a central nervous system sexual response initiator in an amount sufficient to produce genital vasodilation but less than the amount required to produce effective vasocongestive arousal. The preferred central nervous system sexual response initiator is apomorphine or a pharmaceutically acceptable acid addition salt thereof.

1 . A method of normalizing the timing of sexual response in a mammal comprising the administration of an amount of a central nervous system sexual response initiator in an amount sufficient to produce genital vasodilation but less than the amount required to produce effective vasocongestive arousal in said human.  
   
   
       2 . A method in accordance with  claim 1  comprising administering said central nervous system sexual response initiator to said mammal during a period of between about two to about one-hundred-twenty minutes immediately prior to coitus.  
   
   
       3 . A method in accordance with  claim 1  wherein said central nervous system sexual response initiator is selected from such agents which act upon one or more dopaminergic, serotonergic, oxytocinergic or nitroxidergic mid-brain pathways to initiate a sexual response.  
   
   
       4 . A method in accordance with  claim 3  wherein said central nervous system initiator is a compound acting upon the dopaminergic mid-brain pathway selected from the group consisting of apomorphine, bromocriptine, lisuride, methergoline, pergolide, piribidil, and quinpirole or a pharmaceutically acceptable salt or pro-drug thereof.  
   
   
       5 . A method in accordance with  claim 3  wherein said central nervous system initiator is a compound acting upon the serotonergic mid-brain pathway selected from the group consisting of 1-(2,5-dimethoxy-4-iodophenyl)-1-aminopropane, 5-methoxytryptamine, α-methyl-5-hydroxytryptamine, 2-methyl-5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine, buspirone, and sumatriptin or a pharmaceutically acceptable salt or pro-drug thereof.  
   
   
       6 . A method in accordance with  claim 3  wherein said central nervous system initiator is a compound acting upon the oxytocinergic mid-brain pathway selected from the group consisting of isotocin, carbetocin, Lys-conopressin, deaminooxytocin, mesotocin, antocin, glumitocin, aspargitocin, valitocin, asvatocin, phasvatocin, and seritocin.  
   
   
       7 . A method of normalizing the timing of sexual response in a mammal comprising the administration of an amount of apomorphine or a pharmaceutically acceptable salt or pro-drug thereof in an amount sufficient to produce genital vasodilation but less than that required to produce effective vasocongestive arousal in said human.  
   
   
       8 . The method according to  claim 7  wherein said apomorphine or pharmaceutically acceptable salt or pro-drug thereof is administered to said mammal during a period of between about two to about one-hundred-twenty minutes immediately prior to coitus.  
   
   
       9 . The method according to  claim 7  wherein said apomorphine or pharmaceutically acceptable salt or pro-drug thereof is administered to said mammal during a period of between about two to about sixty minutes immediately prior to coitus.  
   
   
       10 . The method according to  claim 7  wherein said apomorphine or pharmaceutically acceptable salt or pro-drug thereof is administered to said mammal in an amount sufficient to produce plasma apomorphine concentrations less than about 0.25 ng/mL.  
   
   
       11 . The method according to  claim 7  wherein said apomorphine or pharmaceutically acceptable salt, ester or pro-drug thereof is administered to said mammal in an amount sufficient to produce plasma apomorphine concentrations of a level ranging between about 0.02 ng/mL to about 0.25 ng/mL.  
   
   
       12 . The method according to  claim 7  further comprising co-administration of an androgen.  
   
   
       13 . The method according to  claim 12  wherein said androgen is selected from the group consisting of testosterone, dihydrotestosterone, and dehydroepiandrostenedione or a pharmaceutically acceptable salt or pro-drug thereof.  
   
   
       14 . The method according to  claim 13  wherein said androgen is testosterone or a pharmaceutically acceptable salt or pro-drug thereof.  
   
   
       15 . A method of prolonging vasocongestive arousal in a mammal comprising administering to said mammal an amount of apomorphine or a pharmaceutically acceptable salt or pro-drug thereof in an amount sufficient to produce plasma concentrations less than about 0.25 ng/mL.  
   
   
       16 . The method according to  claim 15  wherein said apomorphine or pharmaceutically acceptable salt or pro-drug thereof is administered to said human in an amount sufficient to produce plasma apomorphine concentrations of a level ranging between about 0.02 ng/mL to about 0.25 ng/mL.  
   
   
       17 . The method according to  claim 7  wherein said mammal is a human male.  
   
   
       18 . The method according to  claim 17  wherein said human male suffers from sexual arousal disorder.  
   
   
       19 . The method according to  claim 17  wherein said human male suffers from premature ejaculation.  
   
   
       20 . The method according to  claim 18  wherein said apomorphine or pharmaceutically acceptable salt thereof is administered to said human male in an amount sufficient to produce plasma apomorphine concentrations less than about 0.25 ng/mL.  
   
   
       21 . The method according to  claim 18  wherein said apomorphine or pharmaceutically acceptable salt or pro-drug thereof is administered to said human in an amount sufficient to produce plasma apomorphine concentrations of a level ranging between about 0.02 ng/mL to about 0.25 ng/mL.  
   
   
       22 . The method according to  claim 19  wherein said apomorphine or pharmaceutically acceptable salt thereof is administered to said human male in an amount sufficient to produce plasma apomorphine concentrations less than about 0.25 ng/mL.  
   
   
       23 . The method according to  claim 19  wherein said apomorphine or pharmaceutically acceptable salt or pro-drug thereof is administered to said human in an amount sufficient to produce plasma apomorphine concentrations of a level ranging between about 0.02 ng/mL to about 0.25 ng/mL.  
   
   
       24 . The method according to  claim 7  wherein said mammal is a human female.  
   
   
       25 . The method according to  claim 24  wherein said apomorphine or pharmaceutically acceptable salt thereof is administered to said human female in an amount sufficient to produce plasma apomorphine concentrations less than about 0.25 ng/mL.  
   
   
       26 . The method according to  claim 25  wherein said apomorphine or pharmaceutically acceptable salt thereof is administered to said human female in an amount sufficient to produce plasma apomorphine concentrations of a level ranging between about 0.02 ng/mL to about 0.25 ng/mL.  
   
   
       27 . The method according to  claim 23  wherein said human female suffers from sexual arousal disorder.  
   
   
       28 . The method according to  claim 27  wherein said apomorphine or pharmaceutically acceptable salt thereof is administered to said human female in an amount sufficient to produce plasma apomorphine concentrations less than about 0.25 ng/mL.  
   
   
       29 . The method according to  claim 28  wherein said apomorphine or pharmaceutically acceptable salt or pro-drug thereof is administered to said human female in an amount sufficient to produce plasma apomorphine concentrations of a level ranging between about 0.02 ng/mL to about 0.25 ng/mL.  
   
   
       30 . A method of prophylaxis or amelioration of long-term genital organ tissue damage in a mammal comprising the administration of a mammalian central nervous system sexual response initiator in an amount sufficient to cause vasodilation in the genitalia but less than that required to produce an effective vasocongestive arousal in said mammal.  
   
   
       31 . A method in accordance with  claim 30  wherein said central nervous system initiator is selected from compounds which act upon one or more mammalian dopaminergic, serotonergic, oxytocinergic or nitroxidergic mid-brain pathways to initiate a sexual response.  
   
   
       32 . A method in accordance with  claim 31  wherein said central nervous system initiator is a compound acting upon the dopaminergic mid-brain pathway selected from the group consisting of apomorphine, bromocriptine, lisuride, methergoline, pergolide, piribidil, and quinpirole or a pharmaceutically acceptable salt or pro-drug thereof.  
   
   
       33 . A method in accordance with  claim 31  wherein said central nervous system initiator is a compound acting upon the serotonergic mid-brain pathway selected from the group consisting of 1-(2,5-dimethoxy-4-iodophenyl)-1-aminopropane, 5-methoxytryptamine, α-methyl-5-hydroxytryptamine, 2-methyl-5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine, buspirone, and sumatriptin or a pharmaceutically acceptable salt or pro-drug thereof.  
   
   
       34 . A method in accordance with  claim 31  wherein said central nervous system initiator is a compound acting upon the oxytocinergic mid-brain pathway selected from the group consisting of isotocin, carbetocin, Lys-conopressin, deaminooxytocin, mesotocin, antocin, glumitocin, aspargitocin, valitocin, asvatocin, phasvatocin, and seritocin.  
   
   
       35 . A method of ameliorating long-term genital organ tissue damage in a mammal comprising the chronic administration of apomorphine or a pharmaceutically acceptable salt thereof in an amount less than that required to produce effective vasocongestive arousal in said mammal, but sufficient to cause vasodilation in the genitalia.  
   
   
       36 . The method according to  claim 35  wherein said apomorphine or pharmaceutically acceptable salt thereof is administered to said human in an amount sufficient to produce plasma concentration levels less than about 0.25 ng/mL.  
   
   
       37 . The method according to  claim 36  wherein said apomorphine or pharmaceutically acceptable salt thereof is administered to said human in an amount sufficient to produce plasma concentration levels in the range of about 0.02 ng/mL to about 0.25 ng/mL.