Method of treating dyskinesia

Abstract

Methods of treating patients with dyskinesias, by administering a therapeutically effective amount of a dual-action μ-opioid receptor antagonist/κ-opioid receptor agonists or prodrug thereof to a subject in need thereof, sufficient to mitigate the dyskinesia. Alternatively, a combination of both a μ-opioid receptor antagonist or prodrug thereof, and a κ-opioid receptor agonist or prodrug thereof can be administered, either together or separately.

What is claimed is: 
     
         1 . A method of treating or mitigating a dyskinesia, comprising administering to a subject in need thereof a therapeutically effective amount of a dual-action μ-opioid receptor antagonist/κ-opioid receptor agonist. 
     
     
         2 . The method of  claim 1 , wherein said dual action mu-opioid receptor antagonist/kappa-opioid receptor agonist is selected from the group consisting of Nalbuphine, Butorphanol, Pentazocine Nalorphine, Naltriben, Alazocine, Atomoxetine, Bremazocine, Salvinorin A, Samidorphan, Nalmefene, Nalodeine and combinations of two or more thereof, and their prodrugs. 
     
     
         3 . The method of  claim 1 , wherein said dual action mu-opioid receptor antagonist/kappa-opioid receptor agonist is administered to said subject at a dose between 0.001 mg/kg and 3 mg/kg. 
     
     
         4 . The method of  claim 1 , wherein said dual action mu-opioid receptor antagonist/kappa-opioid receptor agonist is administered to said subject in a pharmaceutical composition, wherein said pharmaceutical composition is in a form selected from the group consisting of tablets, capsules, syrups, gels, suppositories, skin patches, inhalable powders, inhalable aerosols, sublingual sprays or sublingual solid dosage form, buccal films, mucoadhesive buccal patches, intranasal sprays and intranasal aerosols, or a form administered through a medical device capable of continuous delivery of a pharmaceutical agent. 
     
     
         5 . The method of  claim 1 , wherein said dual action mu-opioid receptor antagonist/kappa-opioid receptor agonist is Nalbuphine or an ester of Nalbuphine. 
     
     
         6 . The method of  claim 1 , wherein the ester of Nalbuphine is selected from the group consisting of benzoate ester of Nalbuphine and the sebacoyl diester of Nalbuphine. 
     
     
         7 . The method of  claim 1 , wherein the dyskinesia is selected from the group consisting of L-DOPA induced dyskinesia (LID), chorea of Huntington's disease, neuroleptic-induced tardive dyskinesia, and Tourette's syndrome. 
     
     
         8 . The method of  claim 1 , wherein the dyskinesia is in a subject diagnosed with Tourette's syndrome. 
     
     
         9 . The method of  claim 7 , wherein said dyskinesia is in a subject diagnosed with Huntington's disease. 
     
     
         10 . The method of  claim 7 , wherein the dyskinesia is in a subject diagnosed with LID. 
     
     
         11 . The method of  claim 1 , wherein the kappa-opioid receptor agonistic activity at the kappa-opioid receptor is at a K i  ranging from about 0.1 nM to about 100 nM. 
     
     
         12 . The method of  claim 1 , wherein the mu-opioid receptor antagonistic activity at the mu-opioid receptor is at a K i  ranging from about 0.1 nM to about 100 nM. 
     
     
         13 . The method of  claim 11 , wherein the antagonistic activity at the mu-opioid receptor is at a K i  ranging from about 0.12 nM to about 29 nM. 
     
     
         14 . The method of  claim 1 , wherein the dual-action μ-opioid receptor antagonist/κ-opioid receptor agonist is Nalorphine, Pentazocine, Butrophanol or any combinations of two or more thereof. 
     
     
         15 . The method of  claim 1 , wherein the method further includes administration of a second compound selected from the group consisting of amantadine, an adenosine A2a antagonist, an alpha-2 adrenergic antagonist, a dopamine agonist, a monoamine oxidase (MAO) inhibitor, a catechol-O-methyl transferase inhibitor. 
     
     
         16 . The method of  claim 15 , wherein the dual action mu-opioid receptor antagonist/kappa-opioid receptor agonist is Nalbuphine and the second compound is selected from the group consisting of amantadine, fipamezole, L-DOPA, and any combinations thereof Safinamide.