Compositions and uses thereof to ameliorate pain

Abstract

Hydrazinopyridazines, fused hydrazinopyridazines, phenylethylhydrazines, or combinations thereof, compositions comprising hydrazinopyridazines, fused hydrazinopyridazines, phenylethylhydrazines, or combinations thereof, and methods for using them for the treatment of pain are described.

1 - 10 . (canceled) 
     
     
         11 . A composition comprising a fused hydrazinopyridazine or a hydrazinopyridazine in a therapeutically effective amount for treating a patient with pain associated with a spinal cord injury. 
     
     
         12 . The composition according to  claim 11 , wherein the fused hydrazinopyridazine is a compound of the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein:
 R is independently selected in each instance from hydrogen, acyl, or sulfonyl; or alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted; and 
 R A  represents three substituents, each of which is independently selected from the group consisting of hydrogen, halo, hydroxy and derivatives thereof, amino and derivatives thereof, thio and derivatives thereof, acyl, carboxylate or a derivative thereof, hydroxylamino and derivatives thereof, hydrazino and derivatives thereof, sulfonyl or a derivative thereof, or sulfonyl or a derivative thereof; or alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted; and two of R A  are taken together with the attached carbons to form an optionally substituted saturated, unsaturated, or aromatic carbocycle or heterocycle. 
 
       
     
     
         13 . The composition according to  claim 12 , wherein R A  represents a hydrogen; or
 R A  includes an optionally substituted benzo group; or   R A  includes an optionally substituted fused piperidine; or   R A  includes a hydrazino or derivative thereof; or   R A  includes a hydrazino; or   R A  includes amino or a derivative thereof; or   R A  includes dialkylamino, where each alkyl is independently selected, and independently optionally substituted.   
     
     
         14 . The composition according to  claim 12 , wherein each R is hydrogen; or at least one R is acyl; or at least one R is optionally substituted alkoxycarbonyl. 
     
     
         15 . The composition according to  claim 14 , wherein each R is hydrogen. 
     
     
         16 . The composition according to  claim 14 , wherein at least one R is acyl. 
     
     
         17 . The composition according to  claim 14 , wherein at least one R is optionally substituted alkoxycarbonyl. 
     
     
         18 . The composition according to  claim 11 , wherein the fused hydrazinopyridazine is hydralazine. 
     
     
         19 . The composition according to  claim 11 , wherein the composition is formulated for oral administration. 
     
     
         20 . The composition according to  claim 11 , wherein the composition is formulated as a single unit dosage. 
     
     
         21 . The composition according to  claim 11 , wherein the composition is formulated as a divided unit dosage. 
     
     
         22 . The composition according to  claim 11 , wherein the hydrazinopyridazine is a phenylethylhydrazine. 
     
     
         23 . The composition according to  claim 11 , wherein the hydrazinopyridazine is a compound of the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein:
 R is independently selected in each instance from hydrogen, acyl, or sulfonyl; or alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted; and 
 R A  represents three substituents, each of which is independently selected from the group consisting of hydrogen, halo, hydroxy and derivatives thereof, amino and derivatives thereof, thio and derivatives thereof, acyl, carboxylate or a derivative thereof, hydroxylamino and derivatives thereof, hydrazino and derivatives thereof, sulfonyl or a derivative thereof, or sulfonyl or a derivative thereof; or alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted; and two of R A  are taken together with the attached carbons to form an optionally substituted saturated, unsaturated, or aromatic carbocycle or heterocycle. 
 
       
     
     
         24 . The composition according to  claim 23 , wherein R A  represents a hydrogen; or
 R A  includes an optionally substituted benzo group; or   R A  includes an optionally substituted fused piperidine; or   R A  includes a hydrazino or derivative thereof; or   R A  includes a hydrazino; or   R A  includes amino or a derivative thereof; or   R A  includes dialkylamino, where each alkyl is independently selected, and independently optionally substituted.   
     
     
         25 . The composition according to  claim 24 , wherein each R is hydrogen; or at least one R is acyl; or at least one R is optionally substituted alkoxycarbonyl. 
     
     
         26 . The composition according to  claim 25 , wherein each R is hydrogen. 
     
     
         27 . The composition according to  claim 25 , wherein at least one R is acyl. 
     
     
         28 . The composition according to  claim 25 , wherein at least one R is optionally substituted alkoxycarbonyl. 
     
     
         29 . The composition according to  claim 23 , wherein the hydrazinopyridazine is phenelzine.