Compositions comprising alpha-1C specific compounds

Abstract

A method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human α 1C adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human α 1A adrenergic receptor, a human α 1B adrenergic receptor, and a human histamine H 1 receptor, and, binds to a human α 2 adrenergic receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to such α 1C adrenergic receptor. Compounds meeting these criteria are provided.

What is claimed is:  
     
         1 . A method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which: 
 a. binds to a human α 1C  adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human α 1A  adrenergic receptor, a human α 1B  adrenergic receptor, and a human histamine H 1  receptor; and    b. binds to a human α 2  adrenergic receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to such α 1C  adrenergic receptor.    
     
     
         2 . A method of  claim 1 , wherein the compound additionally binds to a calcium channel with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to the α 1C  adrenergic receptor.  
     
     
         3 . A method of  claim 1  or  2 , wherein the compound additionally binds to a dopamine D 2  receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to the α 1C  adrenergic receptor.  
     
     
         4 . A method of  claim 1 ,  2 , or  3 , wherein the compound additionally binds to any serotonin receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to the α 1C  adrenergic receptor.  
     
     
         5 . A method of  claim 1 ,  2 ,  3 , or  4 , wherein the compound additionally binds to a dopamine D 3 , D 4 , or D 5  receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to the α 1C  adrenergic receptor.  
     
     
         6 . A method of  claim 1 ,  2 ,  3 ,  4 , or  5  wherein the compound additionally does not cause orthostatic fall in blood pressure at dosages effective to alleviate benign prostatic hyperplasia.  
     
     
         7 . The method of  claim 6  wherein the compound additionally does not cause orthostatic fall in blood pressure in rats at a dosage of 10 micrograms of compound per kilogram of rat.  
     
     
         8 . A method of  claim 1 , wherein the compound has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         9 . A method of  claim 1 , wherein the compound has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         10 . A method of  claim 1 , wherein the compound has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         11 . A method of  claim 1 , wherein the compound has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         12 . A method of inhibiting contraction of prostate tissue which comprises contacting the prostate tissue with an effective contraction-inhibiting amount of a compound which: 
 a. binds to a human α 1C  adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human α 1A  adrenergic receptor, a human α 1B  adrenergic receptor, and a human histamine H 1  receptor; and    b. binds to a human α 2  adrenergic receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to such α 1C  adrenergic receptor.