Use of Malononitrilamides in Neuropathic Pain

Abstract

Provided herein are compounds and pharmaceutical compositions for use in the treatment of neuropathic pain and the neuropathic pain syndromes.

1 .- 13 . (canceled) 
     
     
         14 . A method for treating neuropathic pain and/or neuropathic pain syndromes in a patient, which comprises administering a pharmaceutical composition comprising a therapeutically effective amount of a malononitrilamide. 
     
     
         15 . The method according to  claim 14 , wherein the patient is a human. 
     
     
         16 . The method according to  claim 14 , wherein the neuropathic pain syndrome is postherpetic neuralgia (caused by Herpes Zoster), root avulsions, painful traumatic mononeuropathy, painful polyneuropathy (particularly due to diabetes), central pain syndromes (potentially caused by virtually any lesion at any level of the nervous system), postsurgical pain syndromes (eg, postmastectomy syndrome, postthoracotomy syndrome, phantom pain), complex regional pain syndrome (reflex sympathetic dystrophy and causalgia), and/or migraine or migraine pain. 
     
     
         17 . The method according to  claim 14 , wherein the neuropathic pain is a central pain syndrome caused by spinal cord injury and/or spinal cord contusion. 
     
     
         18 . The method according to  claim 14 , wherein the type of neuropathic pain is selected from those that have a cause that is selected from the group of the following causes: systemic diseases, diabetic neuropathy; drug-induced lesions, neuropathy due to chemotherapy; traumatic syndrome and entrapment syndrome; lesions in nerve roots and posterior ganglia; neuropathies after HIV infections; neuralgia after Herpes infections; nerve root avulsions; cranial nerve lesions; cranial neuralgias, tri-geminal neuralgia; neuropathic cancer pain; phantom pain; compression of peripheral nerves, neuroplexus and nerve roots; paraneoplastic peripheral neuropathy and ganglionopathy; complications of cancer therapies, chemotherapy, irradiation, and surgical interventions; complex regional pain syndrome; type I lesions (previously known as sympathetic reflex dystrophy); and type II lesions (corresponding approximately to causalgia); migraine and migraine pain; cerebral lesions that are predominantly thalamic; infarction, thalamic infarction or brain stem infarction; cerebral tumors or abscesses compressing the thalamus or brain stem; multiple sclerosis; brain operations, thalamotomy in cases of motoric disorders; spinal cord lesions; spinal cord injuries; spinal cord operations, anterolateral cordotomy; ischemic lesions; anterior spinal artery syndrome; Wallenberg's syndrome; and syringomyelia. 
     
     
         19 . The method according to  14 , wherein the neuropathic pain is a chronic neuropathic pain. 
     
     
         20 . The method according to  14 , wherein said composition is administered at daily dosages between 1 mg-10 g/body, preferable 5 mg-5 g/body and more preferable 10 mg-2 g/body beginning after a damage of the nervous system. 
     
     
         21 . A medical kit suitable for the treatment of a neuropathic pain and/or a neuropathic pain syndrome, comprising:
 (a) printed instructions for administering the compound to the patient having a damage of the nervous system   (b) a malononitrilamide compound, or   (c) a pharmaceutical composition according to claim  12  to  13 .   
     
     
         22 . The method of  claim 14 , wherein the malononitrilamide has the formula 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof. 
       
     
     
         23 . The method of  claim 14 , wherein the compound has the formula 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof. 
       
     
     
         24 . The method of  claim 23 , wherein the tautomer of the compound is the keto or enol form, in particular the keto form 2-cyano-3-oxo-N-[4-(trifluoromethyl) phenyl]-6-heptynamide. 
     
     
         25 . The method of  claim 14 , wherein the stereoisomer of the compound is the R or S enantiomer. 
     
     
         26 . The method of  claim 14 , wherein the compound is used in the treatment of peripheral and/or predominantly peripheral neuropathic pain or central and/or predominantly central neuropathic pain. 
     
     
         27 . The method of  claim 26 , wherein the predominantly peripheral neuropathic pain is of a type that is selected from the following types of neuropathic pain and/or has a cause that is selected from the group of the following causes: systemic diseases, diabetic neuropathy, drug-induced lesions, neuropathy due to chemotherapy; traumatic syndrome and entrapment syndrome; lesions in nerve roots and posterior ganglia; neuropathies after HIV infections; neuralgia after Herpes infections; nerve root avulsions; cranial nerve lesions; cranial neuralgias, trigeminal neuralgia; neuropathic cancer pain; phantom pain; compression of peripheral nerves, neuroplexus and nerve roots; paraneoplastic peripheral neuropathy and ganglionopathy, complications of cancer therapies, chemotherapy, irradiation, and surgical interventions; complex regional pain syndrome; type I lesions (previously known as sympathetic reflex dystrophy); and type II lesions (corresponding approximately to causalgia). 
     
     
         28 . The method of  claim 26 , wherein the predominantly central neuropathic pain is of a type that has a cause that is selected from the following group of causes: cerebral lesions that are predominantly thalamic; infarction, thalamic infarction or brain stem infarction; cerebral tumors or abscesses compressing the thalamus or brain stem; multiple sclerosis; head pain syndrome caused by central pain mechanisms including migraine or migraine pain; brain operations, thalamotomy in cases of motoric disorders; spinal cord lesions; spinal cord injuries; spinal cord operations, anterolateral cordotomy; ischemic lesions; anterior spinal artery syndrome; Wallenberg's syndrome; and syringomyelia. 
     
     
         29 . The method of  claim 14 , wherein the neuropathic pain syndrome is postherpetic neuralgia; root avulsions; painful traumatic mononeuropathy; painful polyneuropathy; central pain syndromes; postsurgical pain syndromes; postmastectomy syndrome; postthoracotomy syndrome; phantom pain; complex regional pain syndrome reflex sympathetic dystrophy and causalgia; and migraine or migraine pain. 
     
     
         30 . The method of  claim 14 , wherein the neuropathic pain is a central pain syndrome caused by spinal cord injury or spinal cord contusion. 
     
     
         31 . The method of  claim 14 , wherein the neuropathic pain is a chronic neuropathic pain. 
     
     
         32 . The method of  claim 14 , wherein the compound is administered at daily dosages between 1 mg-10 g/body, 5 mg-5 g/body or 10 mg-2 g/body beginning after a damage of the nervous system.