Prototypical brain protective activity of tetrahydro-n-methyl-2,2-diphenyl-3-furanomethanamine (ae37met)

Abstract

Tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine (AE37Met) is a highly selective ligand of the extrasynaptic NMDA receptors, of the M2 muscarinic autoreceptors and of the sigma-1 (σ1) receptors, with prototypical brain, preventive and therapeutical, protective activity. This invention concerns the prototypical profile of AE37Met and its pharmaceutically acceptable salts, with cytoprotective activity, more specifically for brain glial cells and neurons, against the neuro-degenerative diseases (e.g. Alzheimer's, Huntington's and Parkinson's diseases, depression, brain ischemia/hypoxia, traumatic brain injury and epilepsy), by the highly selective antagonisms, exerced by AE37Met, on the extrasynaptic NMDA glutamatergic receptors [eNMDA(−)] and on the M2 muscarinic cholinergic autoreceptors [M2(−)], associated with a highly selective sigma-1 agonism [σ1(+)]. The above prototypical profile was observed only with AE37Met between the other family members (AE14, AE37 and their enantiomers).

What is claimed as being new and desired to be protected by Letters Patent of the United States is as follows: 
     
         1 . A compound comprising an effective amount of a compound selected from the group consisting of tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine, pharmaceutically acceptable salts of tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine, enantiomers of tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine, and combinations thereof, said compound being as prototypical selective antagonists of extrasynaptic N-methyl-D-aspartate receptors, [e NMDA (−)], of M2 muscarinic autoreceptors of cholinergic neurons [M2 (−)] and selective agonist of sigma-1 receptors [σ1 (+)], with brain preventive and therapeutical, protective activity. 
     
     
         2 . A pharmaceutical composition comprising an effective amount of a compound and at least one pharmaceutically acceptable excipient, said compound being selected from the group consisting of tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine, pharmaceutically acceptable salts of tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine, enantiomers of tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine, and combinations thereof, said compound being as prototypical [e NMDA (−)], [M2 (−)] and [σ1 (+)] with brain, preventive and therapeutical, protective activity. 
     
     
         3 . A method of using a compound for preparing of pharmaceuticals, said method comprising the steps of:
 preparing an effective amount of a compound selected from the group consisting of tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine, pharmaceutically acceptable salts of tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine, enantiomers of tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine, and combinations thereof, with brain, preventive and therapeutical, protective activity; and   preparing at least one pharmaceutical using said compound.   
     
     
         4 . The method according to  claim 3 , wherein said pharmaceutical with brain, preventive and therapeutical, protective activity against cytodegenerative and neurodegenerative processes in one mild chronic stress brain condition is selected from the group consisting of Alzheimer's disease, Huntington's disease, Parkinson's disease, elderly and depression, said pharmaceutical is administered to an individual at doses of 1 to 10 mgs/day, orally. 
     
     
         5 . The method according to  claim 3 , wherein said pharmaceutical with antidepressive activity associated with neuroprotection against a pathological apoptosis of neurons in depression is administered at doses of 5 to 15 mgs/daily, per os. 
     
     
         6 . The method according to  claim 3 , wherein said pharmaceutical being used against cholinergic adverse effects of IAChEases in the symptomatic treatment of Alzheimer's disease by the antagonism of M2 and M3 muscarinic receptors exerced by said compound at 1 to 10 mgs/daily, per OS. 
     
     
         7 . The method according to  claim 3 , wherein said pharmaceutical being used for valorization of IChEases as therapeutical agents against an evolution of Alzheimer's disease, by highly selective antagonisms of extrasynaptic NMDA receptors and of presynaptic muscarinic M2 cholinergic autoreceptors, completed with a highly selective sigma-1 agonism, exerced by said compound, at 1 to 10 mgs/daily, per os. 
     
     
         8 . The method according to  claim 3 , wherein said pharmaceutical having brain, preventive and therapeutical, protective activity exerced against hard neuronal stress brain pathological states at 10 to 20 mgs/daily, per os, or 5 to 10 mgs, intravenous, against brain ischemic accidents. 
     
     
         9 . The method according to  claim 8 , wherein said hard neuronal stress brain pathological states is selected from the group consisting of epilepsy, and brain ischemia. 
     
     
         10 . The method according to  claim 3 , wherein said pharmaceutical is co-administered to an individual with inhibitors of acetylcholinesterases (IAChEases). 
     
     
         11 . The method according to  claim 10 , wherein said compound is configured to prevent a cholinergic adverse effect of said IAChEases by way of antagonistic effects of said compound.