Alpha conotoxin peptides with analgesic properties

Abstract

This invention relates to novel α-conotoxin-like peptides comprising the following amino acid sequence (SEQ ID NO: 10 ): Xaa 1 -Cys-Cys-Ser-Xaa 2 -Xaa 3 -Xaa 4 -Cys-Xaa 5 -Xaa 6 -Xaa 7 -Xaa 8 -Xaa 9 -Xaa 10 -Xaa 11 -Cys-NH 2 in which Xaa 1 is Gly or Asp; Xaa 3 is Pro, Hyp or Glu; each of Xaa 2 to Xaa 8 and Xaa 11 is independently any amino acid; Xaa 9 is Pro, Hyp or Glu; Xaa 10 is Asp, Glu or γ-carboxyGlu; Xaa 11 is optionally absent; and the C-terminus is optionally amidated, with the proviso that the peptide is not α-conotoxin Ep1 or α-conotoxin Im1. The peptides are useful in the treatment or prevention of pain, in recovery from nerve injury, and in the treatment of painful neurological conditions such as stroke.

1 . A method of treating a condition mediated by a neuronal nicotinic acetylcholine receptor (nAchR) in a subject, comprising administering to a subject in need of such treatment an effective amount an α-conotoxin which is a neuronal nAchR antagonist. 
     
     
         2 . A method according to  claim 1 , in which the condition being treated is selected from the group consisting of stroke, pain, epilepsy, nicotine addiction, schizophrenia, Parkinson's disease, small cell lung carcinoma and Alzheimer's disease. 
     
     
         3 . A method according to  claim 2 , wherein the condition being treated is pain. 
     
     
         4 . A method according to  claim 3 , wherein the pain is neurogenic or neuropathic pain. 
     
     
         5 . A method of treating or preventing pain in a subject, comprising administering to a subject in need of such treatment an effective amount of a neuronal nAchR antagonist. 
     
     
         6 . A method according to  claim 5 , wherein the pain is cancer pain, post-surgical pain, oral or dental pain, pain from referred trigeminal neuralgia, pain from post-herpetic neuralgia, phantom limb pain, pain from fibromyalgia, or pain from reflex sympathetic dystrophy. 
     
     
         7 . A method according to  claim 5 , wherein the pain is a result of, or associated with, an inflammatory condition. 
     
     
         8 . A method according to  claim 7  wherein the inflammatory condition is inflammatory arthritis. 
     
     
         9 . A method according to  claim 8  wherein the arthritis is rheumatoid arthritis or degenerative arthritis. 
     
     
         10 . A method of accelerating recovery from nerve injury in a subject, comprising administering to a subject in need thereof an effective amount of a neuronal nAchR antagonist. 
     
     
         11 . A method according to  claim 1 , wherein the antagonist does not affect muscle-type nicotinic responses. 
     
     
         12 . A method according to  claim 5 , wherein antagonist is an α-conotoxin. 
     
     
         13 . A method according to  claim 10 , wherein the antagonist is an α-conotoxin.