Treatment of motor fluctuations

Abstract

The invention relates to the use of compounds that enhance 5-hydroxytryptamine 1a receptor activity, or activation (e.g. a selective 5-hydroxytryptamine 1a receptor agonists) for preventing or reducing motor fluctuations associated with dopamine replacement therapy.

1 . The a use of a compound which enhances 5-hydroxytryptamine 1a receptor activity, or activation, for the manufacture of a medicament for the prevention or reduction of motor fluctuations associated with dopamine replacement therapy.  
     
     
         2 . The use according to  claim 1 , wherein the compound is a 5-hydroxytryptamine 1a receptor agonist.  
     
     
         3 . The use according to  claim 2 , wherein the compound is a selective 5-hydroxytryptamine 1a receptor agonist.  
     
     
         4 . The use according to  claim 3 , wherein the agonist is selected from the group consisting of: 
 (RS)-trans-8-hydroxy-2-[-n-propyl-N-(3′-iodo-2′-propenyl)amino]tetralin;    (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin;    1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenylpiperazine;    8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,8-dione;    1-(3-chlorophenyl)-4-hexylpiperazine;    (±)-5-methoxy-3-dipropylaminochroman; and    (±)-8-methoxy-2-dipropylaminotetralin.    
     
     
         5 . The use according to any preceding claim, for the treatment of motor fluctuations associated with dopamine replacement therapy for movement disorders.  
     
     
         6 . The use according to  claim 5  wherein the movement disorder is parkinsonism.  
     
     
         7 . The use according to  claim 6  wherein the parkinsonism is idiopathic Parkinson's disease or post-encephalitic parkinsonism.  
     
     
         8 . The use according to  claim 7  wherein the parkinsonism results from head injury, the treatment of schizophrenia, drug intoxication or manganese poisoning.  
     
     
         9 . The use according to any preceding claim wherein the dopamine replacement therapy involves the use of a dopamine receptor agonist.  
     
     
         10 . The use according to  claim 9  wherein the agonist is L-DOPA.  
     
     
         11 . The use according to any preceding claim for prophylactic treatment of motor fluctuations.  
     
     
         12 . The use according to any one of  claims 1  to  10  wherein the efficacy of the dopamine replacement therapy is wearing-off as defined herein.  
     
     
         13 . The use according to any one of  claims 1  to  10  wherein the efficacy of the dopamine replacement therapy is on-off as defined herein.  
     
     
         14 . A method for the prevention or reduction of motor fluctuations associated with dopamine replacement therapy comprising administering to a person or animal in need of such treatment a therapeutically effective amount of a compound that enhances 5-hydroxytryptamine 1a receptor activity, or activation.  
     
     
         15 . The method according to  claim 14  comprising administering a compound as defined in any one of  claims 1  to  13 .