Agent for treatment of schizophrenia

Abstract

The present invention provides a novel method for treatment of schizophrenia which can improve wide-ranging symptoms of schizophrenia, especially positive symptoms and negative symptoms without being accompanied by extrapyramidal symptoms, which comprises orally administering as an active compound (1R,2S,3R,4S)-N-[(1R,2R)-2-[4-(1,2-benzoisothiazol-3-yl)-1-piperazinylmethyl]-1-cyclohexylmethyl]-2,3-bicyclo[2.2.1]heptanedicarboxyimide or a pharmaceutically acceptable salt thereof (e.g., hydrochloride) at a daily dose of 5 mg to 120 mg once a day to a patient with schizophrenia, and a therapeutic agent to be used in said method.

1 . (canceled) 
     
     
         2 . A method of treating psychosis with an antipsychotic agent, comprising:
 selecting an antipsychotic agent that provides incidence of convulsion no greater than that in a placebo-treated group;   orally administering once daily to a patient with psychosis a pharmaceutical composition comprising said antipsychotic agent,   wherein the antipsychotic agent comprises (1R,2S,3R,4S)-N-[(1R,2R)-2-[4-(1,2-benzoisothiazol-3-yl)-1-piperazinylmethyl]-1-cyclohexylmethyl]-2,3-bicyclo[2.2.1]heptanedicarboximide or a pharmaceutically acceptable salt thereof.   
     
     
         3 . The method of  claim 2 , wherein the antipsychotic agent is (1R,2S,3R,4S)-N-[(1R,2R)-2-[4-(1,2-benzoisothiazol-3-yl)-1-piperazinylmethyl]-1-cyclohexylmethyl]-2,3-bicyclo[2.2.1]heptanedicarboximide hydrochloride. 
     
     
         4 . The method of  claim 3 , wherein the method treats schizophrenia in the patient. 
     
     
         5 . The method of  claim 4 , wherein the daily dose is 20 mg. 
     
     
         6 . The method of  claim 4 , wherein the daily dose is 40 mg. 
     
     
         7 . The method of  claim 4 , wherein the daily dose is 60 mg. 
     
     
         8 . The method of  claim 4 , wherein the daily dose is 80 mg. 
     
     
         9 . The method of  claim 4 , wherein the daily dose is 120 mg. 
     
     
         10 . The method of  claim 3 , wherein the method treats manic depressive psychosis in the patient. 
     
     
         11 . The method of  claim 10 , wherein the daily dose is 20 mg. 
     
     
         12 . The method of  claim 10 , wherein the daily dose is 40 mg 
     
     
         13 . The method of  claim 10 , wherein the daily dose is 60 mg. 
     
     
         14 . The method of  claim 10 , wherein the daily dose is 80 mg. 
     
     
         15 . The method of  claim 10 , wherein the daily dose is 120 mg. 
     
     
         16 . A method of treating psychosis with an antipsychotic agent at an incidence of convulsion no greater than that of placebo, comprising:
 selecting and orally administering once daily to a patient with psychosis a pharmaceutical composition comprising an antipsychotic agent, which induces convulsions at a rate no greater than placebo,   wherein the antipsychotic agent comprises (1R,2S,3R,4S)-N-[(1R,2R)-2-[4-(1,2-benzoisothiazol-3-yl)-1-piperazinylmethyl]-1-cyclohexylmethyl]-2,3-bicyclo[2.2.1]heptanedicarboximide or a pharmaceutically acceptable salt thereof.   
     
     
         17 . The method of  claim 16 , wherein the antipsychotic agent is (1R,2S,3R,4S)-N-[(1R,2R)-2-[4-(1,2-benzoisothiazol-3-yl)-1-piperazinylmethyl]-1-cyclohexylmethyl]-2,3-bicyclo[2.2.1]heptanedicarboximide hydrochloride. 
     
     
         18 . The method of  claim 17 , wherein the method treats schizophrenia in the patient. 
     
     
         19 . The method of  claim 18 , wherein the daily dose is 20 mg, 40 mg, 60 mg, 80 mg or 120 mg. 
     
     
         20 - 23 . (canceled) 
     
     
         24 . The method of  claim 17 , wherein the method treats manic depressive psychosis in the patient. 
     
     
         25 . The method of  claim 24 , wherein the daily dose is 20 mg, 40 mg, 60 mg, 80 mg or 120 mg. 
     
     
         26 - 31 . (canceled) 
     
     
         32 . The method of  claim 2 , wherein the treatment is conducted for six weeks. 
     
     
         33 . The method of  claim 3 , wherein the treatment is conducted for six weeks. 
     
     
         34 . The method of  claim 16 , wherein the treatment is conducted for six weeks. 
     
     
         35 . The method of  claim 17 , wherein the treatment is conducted for six weeks. 
     
     
         36 . The method of  claim 19 , wherein the treatment is conducted for six weeks. 
     
     
         37 . The method of  claim 25 , wherein the treatment is conducted for six weeks. 
     
     
         38 . A method of treating psychosis with an antipsychotic agent, comprising:
 selecting an antipsychotic agent that does not induce convulsions in patients at a greater occurrence than the occurrence of convulsions in psychotic patients not treated with antipsychotic agent; and   orally administering once daily a pharmaceutical composition comprising said antipsychotic agent to a patient with psychosis,   wherein the antipsychotic agent administered is (1R,2S,3R,4S)-N-[(1R,2R)-2-[4-(1,2-benzoisothiazol-3-yl)-1-piperazinylmethyl]-1-cyclohexylmethyl]-2,3-bicyclo[2.2.1]heptanedicarboximide hydrochloride; and   wherein the psychosis is schizophrenia or manic depressive psychosis.   
     
     
         39 . The method of  claim 38 , wherein the daily dose is 20 mg, 40 mg, 60 mg, 80 mg or 120 mg. 
     
     
         40 . The method of  claim 38 , wherein the treatment is conducted for six weeks. 
     
     
         41 . The method of  claim 39 , wherein the treatment is conducted for six weeks.