Use of substance P antagonists for the treatment of chronic fatigue syndrome and/or fibromyalgia and use of NK-1 receptor antagonists for the treatment of chronic fatigue syndrome

Abstract

The invention relates to the pharmaceutical use of specific substance P antagonists, in particular 1-acylpiperidine substance P antagonists, especially N-benzoyl-2-benzyl-4-(azanaphthoyl-amino)-piperidines, e.g. of formula wherein X and Y are each independently of the other N and/or CH and the ring A is unsubstituted or mono- or poly-substituted by substituents selected from the group consisting of lower alkyl, lower alkoxy, halogen, nitro and trifluoromethyl; and pharmnaceutically acceptable salts thereof for treatment of chronic fatigue syndrome (CFS) in the absence of serotonin agonist/selective serotonin reuptake inhibitory therapy, or for the treatment of fibromyalgia or associated functional symptoms.

1 . Use of a specific substance P antagonist or a pharmaceutically acceptable salt thereof in the treatment of chronic fatigue syndrome in the absence of serotonin agonist/selective serotonin reuptake inhibitory therapy; or use of a substance P antagonist or a pharmaceutically acceptable salt thereof, devoid of substantial serotonin agonist activity, in the treatment of chronic fatigue syndrome in the absence of selective serotonin reuptake inhibiting activity; or use of a specific substance P antagonist or a pharmaceutically acceptable salt thereof as mono-therapy in the treatment of chronic fatigue syndrome.  
     
     
         2 . Use of a specific substance P antagonist or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the treatment of chronic fatigue syndrome in the absence of serotonin agonist/selective serotonin reuptake inhibitory therapy; or use of a substance P antagonist or a pharmaceutically acceptable salt thereof, devoid of substantial serotonin agonist activity, for the preparation of a medicament for the treatment of chronic fatigue syndrome in the absence of selective serotonin re-uptake inhibiting activity; or use of a specific substance P antagonist or a pharmaceutically acceptable thereof for preparation of a medicament for use as monotherapy in the treatment of chronic fatigue syndrome.  
     
     
         3 . A method for treatment of CFS or fibromyalgia or associated functional symptoms of fibromyalgia in a patient comprising administering to said patient an effective amount of a 1-acylpiperidine substance P antagonist or a pharmaceutically acceptable salt thereof; or  
     
     
         4 . The use of a 1-acylpiperidine substance P antagonist or a pharmaceutically acceptable salt thereof for the preparation of a medicament for treatment of CFS, or fibromyalgia or associated functional symptoms of fibromyalgia.  
     
     
         5 . A pharmaceutical composition for treatment of CFS or fibromyalgia or associated functional symptoms of fibromyalgia which comprises a 1-acylpiperidine substance P antagonist or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable excipient, diluent or carrier.  
     
     
         6 . A method according to  claim 3 , a use according to  claim 4 , or a composition according to  claim 5 , in which the 1-acylpiperidine is a compound of the formula  
       
         
           
           
               
               
           
         
       
       wherein X and Y are each independently of the other N and/or CH and the ring A is unsubstituted or mono- or poly-substituted by substituents selected from the group consisting of lower alkyl, lower alkoxy, halogen, nitro and trifluoromethyl; or a salt thereof.  
     
     
         7 . A method according to  claim 3 , a use according to  claim 4 , or composition according to  claim 5  in which the 1-acylpiperidine compound is an N-benzoyl-2-benzyl-4-azanaphthoyl-amino-piperidine compound selected from the group consisting of 
 (2R,4S)-N-[1-(3,5-bisfluoromethyl-benzoyl)-2-(4-chlorobenzyl)-piperidin-4-yl]-4-oxo-4H-1-benzopyran-2-carboxamide;  
 (2R,4S)-N-[1-(3,5-bisfluoromethyl-benzoyl)-2-benzyl-piperidin-4-yl]-4-oxo-4H-1-benzopyran-2-carboxamide;  
 (2R,4S)-N-[1-(3,5-bisfluoromethyl-benzoyl)-2-(4-chlorobenzyl)-piperidin-4-yl]-6-fluoro-4-oxo-4H-1-benzopyran-2-carboxamide;  
 (2R,4S)-N-[1-(3,5-bis-trifluoromethyl-benzoyl)-2-benzyl-piperidin-4-yl]-quinoline-4-carboxamide;  
 (2R,4S)-N-[1-(3,5-bis-trifluoromethyl-benzoyl)-2-benzyl-piperidin-4-yl]-quinazoline-4-carboxamide;  
 (2R,4S)-N-[1-(3,5-bis-trifluoromethyl-benzoyl)-2-(4-chloro-benzyl)-piperidin-4-yl]-quinoline-4-carboxamide;  
 (2R,4S)-N-[1-(3,5-bis-trifluoromethyl-benzoyl)-2-(4-chloro-benzyl)-piperidinyl]-quinazoline-4-carboxamide;  
 (2R,4S)-N-[1-(3,5-bis-trifluoromethyl-benzoyl)-2-(4-chloro-benzyl)-piperidinyl]-isoquinoline-1-carboxamide;  
 (2R,4S)-N-[1-(3,5-bis-trifluoromethyl-benzoyl)-2-(4-nitro-benzyl)-piperidinyl]-quinazoline-4-carboxamide;  
 or in each case a salt thereof.  
 
     
     
         8 . Use of an NK-1 receptor antagonist in the treatment of chronic fatigue syndrome; or use of an NK-1 receptor antagonist for the preparation of a medicament for the treatment of chronic fatigue syndrome.