Treatment of depressive disorders

Abstract

The invention provides for the use of carbonic anhydrase activators; protein kinase C activators and FGF-18 to treat depressive disorders. The invention also relates to improved animal models and methods for screening and identifying compounds the treatment of depressive disorders.

1 .- 46 . (canceled) 
     
     
         47 . A method of treating a depressive disorder in a subject in need thereof, comprising administering an effective amount of a composition comprising a protein kinase C (PKC) activator and a pharmaceutically acceptable carrier, wherein the PKC activator is chosen from FGF-18, macrocyclic lactones, benzolactams, pyrrolidinones, bryologs, diacylglycerol derivatives other than phorbol esters, isoprenoids, daphnane-type diterpenes, bicyclic triterpenoids, napthalenesulfonamides, lineolic acid derivatives, diacylglycerol kinase inhibitors, growth factor activators, and any combination thereof. 
     
     
         48 . The method of  claim 47 , wherein the bryologs are chosen from B-ring bryologs and A-ring bryologs. 
     
     
         49 . The method of  claim 47 , wherein the bryolog is a compound with a formula: 
       
         
           
           
               
               
           
         
       
     
     
         50 . The method of  claim 47 , wherein the bryolog is a compound with a formula: 
       
         
           
           
               
               
           
         
       
     
     
         51 . The method of  claim 48 , wherein the B-ring byrologs are chosen from 
       
         
           
           
               
               
           
         
       
     
     
         52 . The method of  claim 48 , wherein the A-Ring analogs are chosen from 
       
         
           
           
               
               
           
         
         wherein R is t-Bu, Ph, or (CH 2 ) 3 p-Br-Ph. 
       
     
     
         53 . The method of  claim 47 , wherein the diacylglycerol derivatives are chosen from unsaturated fatty acids. 
     
     
         54 . The method of  claim 53 , wherein the fatty acids are in a 1,2-sn configuration. 
     
     
         55 . The method of  claim 53 , wherein the fatty acids are cis-unsaturated fatty acids. 
     
     
         56 . The method of  claim 47 , wherein the PKC activator is octylindolactam V. 
     
     
         57 . The method of  claim 47 , wherein the daphnane-type diterpenes are chosen from gnidimacrin, ingenol, ingenol 3,20-dibenzoate, and ingenol-3-angelate. 
     
     
         58 . The method of  claim 47 , wherein the bicyclic triterpenoid is iripallidal. 
     
     
         59 . The method of  claim 47 , wherein the napthalenesulfonamide is N-(n-heptyl)-5-chloro-1-napthalenesulfonamide or N-(6-Phenylhexyl)-5-chloro-1-naphthalenesulfonamide. 
     
     
         60 . The method of  claim 47 , wherein the lineolic acid derivative is 2-[(2-pentylcyclopropyl)methyl]-cyclopropaneoctanoic acid. 
     
     
         61 . The method of  claim 47 , wherein the diacylglycerol kinase inhibitors are chosen from 6-(2-(4-[(4-fluorophenyl)phenylmethylene]-1-piperidinyl)ethyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one and [3-[2-[4-(bis-(4-fluorophenyl)methylene]piperidin-1-yl)ethyl]-2,3-dihydro-2-thioxo-4(1H)-quinazolinone. 
     
     
         62 . The method of  claim 47 , wherein the growth factor activators are chosen from 4-methyl catechol derivatives. 
     
     
         63 . The method of  claim 62 , wherein the 4-methylcatechol derivative is 4-methylcatechol acetic acid. 
     
     
         64 . The method of  claim 47 , wherein the macrocyclic lactones are chosen from neristatins. 
     
     
         65 . The method of  claim 64 , wherein the neristatin is neristatin-1.