Application of r-ketamine and salt thereof as pharmaceuticals

Abstract

Provided is a novel compound having rapid and long-lasting therapeutic effects on diseases exhibiting depressive symptoms. Specifically, provided are an agent for prevention and/or treatment of a depressive symptom, consisting of R(−)-ketamine or a pharmacologically acceptable salt thereof, and a pharmaceutical composition for prevention and/or treatment of a depressive symptom, comprising R(−)-ketamine or a pharmacologically acceptable salt thereof in an effective amount for reducing a depressive symptom, and being substantially free of S(+)-ketamine, and a pharmacologically acceptable salt thereof.

1 - 18 . (canceled) 
     
     
         19 . A method of treating a depressive symptom, comprising administering a derivative of R(−)-ketamine or a pharmacologically acceptable salt thereof to a subject, wherein the derivative of R(−)-ketamine is represented by Formula (I): 
       
         
           
           
               
               
           
         
         wherein the chlorine molecule is substituted for another halogen molecule, the methyl group is substituted for another alkyl group, or a combination thereof. 
       
     
     
         20 . The method of  claim 19 , wherein the derivative of R(−)-ketamine is substantially free of S(+)-ketamine, a derivative of S(+)-ketamine, or a pharmacologically acceptable salt thereof. 
     
     
         21 . The method of  claim 20 , wherein the derivative of R(−)-ketamine comprises no S(+)-ketamine, or the pharmacologically acceptable salt thereof. 
     
     
         22 . The method of  claim 20 , wherein the derivative of R(−)-ketamine comprises an amount of S(+)-ketamine, the derivative or pharmacologically acceptable salt thereof such that side effects of the S(+)-ketamine, derivative or the pharmacologically acceptable salt thereof are not exhibited. 
     
     
         23 . The method of  claim 22 , wherein the side effects comprise psychotomimetic effects. 
     
     
         24 . The method of  claim 19 , wherein the subject has been diagnosed with having a depressive symptom. 
     
     
         25 . The method of  claim 19 , wherein the subject has depression, obsessive-compulsive disorder, posttraumatic stress disorder, major depressive disorder, bipolar disorder, dementia, suicidal ideation, low motivation, mood depression, anxiety, insomnia, or anorexia. 
     
     
         26 . The method of  claim 25 , wherein the dementia is Alzheimer's disease, vascular dementia, or a combination thereof. 
     
     
         27 . The method of  claim 19 , wherein the subject is a child or an adult. 
     
     
         28 . The method of  claim 27 , wherein the adult is an elderly adult. 
     
     
         29 . The method of  claim 19 , wherein the derivative of R(−)-ketamine is administered in a therapeutically effective amount to treat the depressive symptom. 
     
     
         30 . The method of  claim 29 , wherein the therapeutically effective amount is about 0.01 mg/day to about 500 mg/day, about 0.1 mg/day to about 500 mg/day, or about 0.1 mg/day to about 100 mg/day. 
     
     
         31 . The method of  claim 29 , wherein the derivative of R(−)-ketamine is therapeutically effective for 24 hours, 48 hours, 6 days or 7 days after administration to the subj ect. 
     
     
         32 . The method of  claim 19 , wherein the derivative of R(−)-ketamine is formulated in a pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 
     
     
         33 . The method of  claim 32 , wherein the pharmaceutical composition is suitable for intravenous, intramuscular, subcutaneous, transnasal, oral, rectal or transdermal administration. 
     
     
         34 . The method of  claim 34 , wherein the derivative of R(−)-ketamine is formulated a liquid, solution, suspension, powder, tablet, coated tablet, capsule, troche, cream, suppository, gel, patch, liniment or aerosol. 
     
     
         35 . A pharmaceutical composition, comprising a derivative of R(−)-ketamine or a pharmacologically acceptable salt thereof, wherein the derivative of R(−)-ketamine is represented by Formula (I): 
       
         
           
           
               
               
           
         
         wherein the chlorine molecule is substituted for another halogen molecule, the methyl group is substituted for another alkyl group, or a combination thereof. 
       
     
     
         36 . The pharmaceutical composition of  claim 35 , wherein the derivative of R(−)-ketamine is substantially free of S(+)-ketamine, a derivative of S(+)-ketamine, or a pharmacologically acceptable salt thereof. 
     
     
         37 . The pharmaceutical composition of  claim 35 , wherein the derivative of R(−)-ketamine comprises no S(+)-ketamine, or the pharmacologically acceptable salt thereof. 
     
     
         38 . The pharmaceutical composition of  claim 35 , wherein the derivative of R(−)-ketamine comprises an amount of S(+)-ketamine, the derivative or pharmacologically acceptable salt thereof such that side effects of the S(+)-ketamine, derivative or the pharmacologically acceptable salt thereof are not exhibited. 
     
     
         39 . The pharmaceutical composition of  claim 35 , wherein the pharmaceutical composition is suitable for intravenous, intramuscular, subcutaneous, transnasal, oral, rectal or transdermal administration. 
     
     
         40 . The pharmaceutical composition of  claim 35 , wherein the derivative of R(−)-ketamine is formulated a liquid, solution, suspension, powder, tablet, coated tablet, capsule, troche, cream, suppository, gel, patch, liniment or aerosol. 
     
     
         41 . A method of treating a depressive symptom, comprising administering R(−)-ketamine, a derivative of R(−)-ketamine, or a pharmacologically acceptable salt thereof to a subject,
 wherein the subject has been diagnosed with having a depressive symptom, in an amount effective to treat the depressive symptom, and being substantially free of S(+)-ketamine and pharmacologically acceptable salts thereof, 
 wherein the derivative of R(−)-ketamine is represented by Formula (I): 
 
       
         
           
           
               
               
           
         
         wherein the chlorine molecule is substituted for another halogen molecule, the methyl group is substituted for another alkyl group, or a combination thereof. 
       
     
     
         42 . The method of  claim 41 , wherein the chlorine molecule of Formula (I) is substituted for another halogen molecule. 
     
     
         43 . The method of  claim 41 , wherein the methyl group of Formula (I) is substituted for another alkyl group. 
     
     
         44 . The method of  claim 41 , wherein the chlorine molecule of Formula (I) is substituted for another halogen molecule, and the methyl group of Formula (I) is substituted for another alkyl group.