Prophylactic and therapeutic composition for circulatory disorders and method of treatment

Abstract

A prophylactic and therapeutic agent for circulatory disorders, comprising a pyrazolone derivative of the formula: <IMAGE> wherein R1 represents a hydrogen atom, an aryl group, an alkyl group having 1 to 5 carbon atoms or an alkoxycarbonylalkyl group having a total carbon number of 3 to 6; R2 represents a hydrogen atom, an aryloxy group, an arylmercapto group, an alkyl group having 1 to 5 carbon atoms or hydroxyalkyl group having 1 to 3 carbon atoms or R1 and R2 taken together represent an alkylene group having 3 to 5 carbon atoms; R3 represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, a cycloalkyl group having 5 to 7 carbon atoms, a hydroxyalkyl group having 1 to 3 carbon atoms, a benzyl group, a naphthyl group, or a phenyl group which is unsubstituted or substituted with 1 to 3 substituents which are the same or different selected from the group consisting of alkyl groups having 1 to 5 carbon atoms, alkoxy groups having 1 to 5 carbon atoms, hydroxyalkyl groups having 1 to 3 carbon atoms, alkoxycarbonyl groups having total carbon number of 2 to 5, alkylmercapto groups having 1 to 3 carbon atoms, alkylamino groups having 1 to 4 carbon atoms, dialkylamino groups having total carbon number of 2 to 8, halogen atoms, trifluoromethyl group, carboxyl group, cyano group, hydroxyl group, nitro group, amino group and acetamide group, or a pharmaceutically acceptable salt thereof as an active ingredient. The agent of the present invention is useful as a prophylactic and therapeutic agent for circulatory disorders, particularly as an inhibitor against lipid peroxidation and/or an agent for normalizing cerebral dysfunctions.

We claim: . .1. A prophylactic and therapeutic pharmaceutical composition for inhibiting lipid peroxidation by active oxygen, which results from ischemia, comprising: 
     
        carrier..!.2. A method for inhibiting the formation of peroxidized lipids in a mammal, as a result of ischemia, comprising administering an effective amount of a pyrazolone derivative of the formula: ##STR59## wherein R 1  represents a hydrogen atom, an aryl group, an alkyl group having 1 to 5 carbon atoms; R 2  represents a hydrogen atom, an aryloxy group, an alkyl group having 1 to 5 carbon atoms; or R 1  and R 2  taken together represent an alkylene group having 3 to 5 carbon atoms; R 3  represents a cycloalkyl group having 5 to 7 carbon atoms, a naphthyl group, or a phenyl group which is unsubstituted or para or meta substituted with 1 to 3 substituents which are the same or different selected from the group consisting of alkyl groups having 1 to 5 carbon atoms, alkoxy groups having 1 to 5 carbon atoms, alkoxycarbonyl groups having a total carbon number of 2 to 5, alkylmercapto groups having 1 to 3 carbon atoms, halogen atoms, a trifluoromethyl group, a carboxyl group, a cyano group, a hydroxyl group, a nitro group or a pharmaceutically acceptable salt thereof as an active ingredient in a pharmaceutical 
     
     
        carrier. . .3.  A prophylactic and therapeutic pharmaceutical composition for inhibiting the formation of peroxidized lipids in a mammal and simultaneously providing antagonistic action against drowsy pattern in an electroencephalogram caused by barbituates, comprising an effective amount of a pyrazolone derivative of the formula: ##STR60## wherein R 1  represents a hydrogen atom, an aryl group, an alkyl group having 1 to 5 carbon atoms; R 2  represents a hydrogen atom, an aryloxy group, an alkyl group having 1 to 5 carbon atoms; or R 1  and R 2  taken together represent an alkylene group having 3 to 5 carbon atoms; R 3  represents a cycloalkyl group having 5 to 7 carbon atoms, a naphthyl group, or a phenyl group which is unsubstituted or para or meta substituted with 1 to 3 substituents which are the same or different selected from the group consisting of alkyl groups having 1 to 5 carbon atoms, alkoxy groups having 1 to 5 carbon atoms, alkoxycarbonyl groups having a total carbon number of 2 to 5, alkylmercapto groups having 1 to 3 carbon atoms, halogen atoms, a trifluoromethyl group, a carboxyl group, a cyano group, a hydroxyl group, a nitro group or a pharmaceutically acceptable salt thereof as an active ingredient in a pharmaceutical 
     
     
        carrier..!.4. A method for inhibiting the formation of peroxidized lipids in a mammal and simultaneously to provide antagonistic action against drowsy pattern in an electroencephalogram caused by barbituates, comprising administering an effective amount of a pyrazolone derivative of the formula: ##STR61## wherein R 1  represents a hydrogen atom, an aryl group, an alkyl group having 1 to 5 carbon atoms; R 2  represents a hydrogen atom, an aryloxy group, an alkyl group having 1 to 5 carbon atoms; or R 1  and R 5  taken together represent an alkylene group having 3 to 5 carbon atoms; R 3  represents a cycloalkyl group having 5 to 7 carbon atoms, a naphthyl group, or a phenyl group which is unsubstituted or para or meta substituted with 1 to 3 substituents which are the same or different selected from the group consisting of alkyl groups having 1 to 5 carbon atoms, alkoxy groups having 1 to 5 carbon atoms, alkoxycarbonyl groups having a total carbon number of 2 to 5, alkylmercapto groups having 1 to 3 carbon atoms, halogen atoms, a trifluoromethyl group, a carboxyl group, a cyano group, a hydroxyl group, a nitro group or a pharmaceutically acceptable salt thereof as an active ingredient in a pharmaceutical 
     
     
        carrier. . .5.  The composition according to claim 1 or 3, wherein the aryl group represented by R 1  is a phenyl group or phenyl groups which are substituted with a methyl group, a butyl group, a methoxy group, a butoxy group, a hydroxyl group or a chlorine atom; the alkyl group having 1 to 5 carbon atoms represented by R 1 , R 2  or R 3  is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group or a pentyl group; the alkoxycarbonylalkly group having total carbon number of 3 to 6 represented by R 1  is a methoxycabonylmethyl group, an ethoxycarbonylmethyl group, a propoxycarbonylmethyl group, a methoxycarbonylethyl group or a methoxycarbonylpropyl group; the aryloxy group represented by R 2  is a phenoxy group, a p-methylphenoxy group, a p-methoxyphenoxy gorup, a p-chlorophenoxy group or a p-hydroxyphenoxy group; the arylmercapto group represented by R 2  is a phenylmercapto group, a p-methylphenylmercapto group, a p-methoxyphenylmercapto group, a p-chlorophenylmercapto group or a p-hydroxphenylmercapto group; the hydroxyalkyl group having 1 to 3 carbon atoms represented by R 2  R 3  is a hydroxymethyl group, a 2-hydroxyethyl group or a 3-hydroxpropyl group; the cycloalkyl group having 5 to 7 carbon atoms represented by R 3  is a cyclopentyl group, a cyclohexyl group or a cycloheptyl group; as the substituent for the phenyl group in the definition of R 3 , the alkoxy group having 1 to 5 carbon atoms is a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group or a pentyloxy group; the alkoxycarbonyl group having a total carbon number of 2 to 5 is a methoxycarbonyl group, an ethyoxycarbonyl group, a propoxycarbonyl group or a butoxycarbonyl group; the alkylmercapto group having 1 to 3 carbon atoms is a methylmercapto group, an ethylmercapto group or a propylmercapto group; the alkylamino group having 1 to 4 carbon atoms is a methylamino group, an ethylmino group, a propylamino group or a butylamino group and the dialkylamino group having a total carbon number of 2 to 8 is a diemthylamino group, a diethylamino group, a dipropylamino group or a dibutylamino group..!.. .6. The composition according to claim 1 or 3, wherein said pyrazolone derivative is selected from the group consisting of, 3-Methyl-1-phenyl-2-pyrazolin-5-one;   3-Methyl-1-(4-methylphenyl)-2-pyrazolin-5-one;   1-(4-Methoxyphenyl)-3-methyl-2-pyrazolin-5-one;   1-(4-Ethoxyphenyl)-3-methyl-2-pyrazolin-5-one;   1-(4-Chlorophenyl)-3-methyl-2-pyrazolin-5-one;   1-Phenyl-3-propyl-3-pyrazolin-5-one;   3,4-Dimethyl-1-phenyl-2-pyazolin-5-one,   4-Isobutyl-3-methyl-1-phenyl-2-pyrazolin-5-one;   3,3a,4,5,6,7-Hexahydro-2-phenyl-2H-indazol-3-one; and   1-Cyclohexyl-3-methyl-2-pyazolin-5-one or a pharmaceutically acceptable salt thereof..!.. .7. The composition according to claim 1 or 3, wherein said circulatory disorders are ischematic diseases..!.. .8. The composition according to claim 1 or 3, wherein said agent is useful as an inhibitor against lipid peroxidtion..!.. .9. The composition according to claim 1 or 3, wherein 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof as an active ingredient is useful as an agent for normalizing     
     
     
        cerebral functions..!.10. The method of claim 2 or 4, wherein said 
     
     
        pyrazolone derivative is 3-methyl-1-phenyl-2-pyrazolin-5-one. 11. The method of claim 2 or 4, wherein said pyrazolone derivative is 
     
     
        3-methyl-1-(4-methylphenyl)-2-pyrazolin-5-one. 12. The method of claim 2 or 4, wherein said pyrazolone derivative is 
     
     
        1-(4-methoxyphenyl)-3-methyl-2-pyrazolin-5-one. 13. The method of claim 2 or 4, wherein said pyrazolone derivative is 
     
     
        (4-ethoxyphenyl)-3-methyl-2-pyrazolin-5-one. 14. The method of claim 2 or 4, wherein said pyrazolone derivative is 
     
     
        1-(4-chlorophenyl)-3-methyl-2-pyrazolin-5-one. 15. The method of claim 2 or 4, wherein said pyrazolone derivative is 
     
     
        1-phenyl-3-propyl-2-pyazolin-5-one. 16. The method of claim 2 or 4, wherein said pyrazolone derivative is 
     
     
        3,4-dimethyl-1-phenyl-2-pyazolone-5-one. 17. The method of claim 2 or 4, wherein said pyrazolone derivative is 
     
     
        4-isobutyl-3-methyl-1-phenyl-2-pyrazolin-5-one. 18. The method of claim 2 or 4, wherein said pyrazolone derivative is 
     
     
        3,3a,4,5,6,7-hexahydro-2-phenyl-2H-indazol-3-one. 19. The method of claim 2 or 4, wherein said pyrazolone derivative is 1-cyclohexyl-3-methyl-2-pyrazolin-5-one. .Iadd.20. A pharmaceutical composition comprising 1-100 mg/kg of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for cerebral, cardiac or peripheral 
     
     
        circulatory disorders in mammals. .Iaddend..Iadd.21.  A pharmaceutical composition according to claim 20 wherein said disorder is myocardial infarction or cardiac insufficiency. .Iaddend..Iadd.22. A pharmaceutical composition according to claim 20 wherein said disorder is cerebral ischemia. .Iaddend..Iadd.23. A pharmaceutical composition according to claim 20 wherein said disorder is cerebral infarction, cerebral embolism or subarachidonic hemorrhage. .Iaddend..Iadd.24. A pharmaceutical composition comprising 1-100 mg/kg of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for the treatment of trauma in mammals. .Iaddend..Iadd.25. A pharmaceutical composition comprising 1-100 mg/kg of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for the prevention of the recurrence of cerebrovascular disorders in mammals. .Iaddend..Iadd.26. A pharmaceutical composition comprising 1-100 mg/kg of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for 
     
     
        mammals during the emergence from anesthesia. .Iaddend..Iadd.27.  A pharmaceutical composition comprising 1-100 mg/kg of a pyrazolone derivative to provide a prophylactic and therapeutic action for cerebral, cardiac or peripheral circulatory disorders in mammals, said derivative having the formula: ##STR62## wherein R 1  represents a hydrogen atom, an aryl group, an alkyl group having 1 to 5 carbon atoms; R 2  represents a hydrogen atom, an aryloxy group, an alkyl group having 1 to 5 carbon atoms; or R 1  and R 2  taken together represent an alkylene group having 3 to 5 carbon atoms; R 3  represents a cycloalkyl group having 5 to 7 carbon atoms, a naphthyl group, or a phenyl group which is unsubstituted or para or meta substituted with 1 to 3 substituents which are the same or different selected from the group consisting of alkyl groups having 1 to 5 carbon atoms, alkoxy groups having 1 to 5 carbon atoms, alkoxycarbonyl groups having a total carbon number of 2 to 5, alkylmercapto groups having 1 to 3 carbon atoms, halogen atoms, a trifluoromethyl group, a carboxyl group, a cyano group, a hydroxyl group, and a nitro group; or a pharmaceutically 
     
     
        acceptable salt thereof in a pharmaceutical carrier. .Iaddend..Iadd.28.  A pharmaceutical composition in accordance with claim 27, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for cerebral, cardiac or peripheral circulatory disorders accompanied by an ischemic disease. .Iaddend..Iadd.29. A pharmaceutical composition in accordance with claim 28, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for a peripheral circulatory disorder accompanied by an ischemic disease. .Iaddend..Iadd.30. A pharmaceutical composition in accordance with claim 27, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for myocardial ischemia or angina pectoris accompanied by an ischemic disease. .Iaddend..Iadd.31. A pharmaceutical composition in accordance with claim 27, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for a disorder a cerebrovascular disorder or a lowering in cerebral functions accompanied by an ischemic disease. .Iaddend..Iadd.32. A pharmaceutical composition in accordance with claim 27, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for a disorder selected from the group consisting of cerebral apoplexy, cerebral infarction, ischemic cerebrovascular disorders, subarachnoidic hemorrhage, intracerebral hemorrhage, cerebral embolism, cerebral edema, trauma, vascular dementia, cerebrovascular tissue lesion, cerebral arteriosclerosis and obnubilation. .Iaddend..Iadd.33. A pharmaceutical composition in accordance with claim 27 wherein the aryl group represented by R 1  is a phenyl group or phenyl groups which are substituted with a methyl group, a butyl group, a methoxy group, a butoxy group, a hydroxyl group or a chlorine atom; the alkyl group having 1 to 5 carbon atoms represented by R 1  or R 2  is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group or a pentyl group; the aryloxy group represented by R 2  is a phenoxy group, a p-methylphenoxy group, a p-methoxphenoxy group, a p-chlorophenoxy group or a p-hydroxyphenoxy group; the cycloalkyl group having 5 to 7 carbon atoms represented by R 3  is a cyclopentyl group, a cyclohexyl group or a cycloheptyl group; as the substituent for the phenyl group in the definition of R 3 , the alkoxy group having 1 to 5 carbon atoms is a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group or a pentyloxy group; the alkoxycarbonyl group having a total carbon number of 2 to 5 is a methoxycarbonyl group, an ethyoxycarbonyl group, a propoxycarbonyl group or a butoxycarbonyl group; the alkylmercapto group having 1 to 3 carbon atoms is a methylmercapto group, an ethylmercapto group or a propylmercapto group. .Iaddend..Iadd.34. A pharmaceutical composition in accordance with claim 27 wherein said pyrazolone derivative is selected from the group consisting of: 3-Methyl-1-phenyl-2-pyrazolin-5-one;   3-Methyl-1-(4-methylphenyl)-2-pyrazolin-5-one;   1-(4-Methoxyphenyl)-3-methyl-2-pyrazolin-5-one;   1-(4-Ethoxyphenyl)-3-methyl-2-pyrazolin-5-one;   1-(4-Chlorophenyl)-3-methyl-2-pyrazolin-5-one;   1-Phenyl-3-propyl-3-pyrazolin-5-one;   3,4-Dimethyl-1-phenyl-2-pyrazolin-5-one;   4-Isobutyl-3-methyl-1-phenyl-2-pyrazolin-5-one;   3,3a,4,5,6,7-Hexahydro-2-phenyl-2H-indazol-3-one; and   1-Cyclohexyl-3-methyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof. .Iaddend..Iadd.35. A pharmaceutical composition in accordance with claim 27, said composition comprising an effective amount of the pyrazolone to act as an inhibitor against lipid peroxidation. .Iaddend..Iadd.36. A pharmaceutical composition in accordance with claim 27 wherein 3 methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof is useful as an agent for normalizing cerebral functions. .Iaddend..Iadd.37. A method for providing a therapeutic action comprising administering an effective amount of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for cerebral, cardiac or peripheral     
     
     
        circulatory disorders in mammals. .Iaddend..Iadd.38.  A method according to claim 37 wherein said disorder is myocardial infarction or cardiac insufficiency. .Iaddend..Iadd.39. A method according to claim 37 wherein said disorder is cerebral ischemia. .Iaddend..Iadd.40. A method according to claim 37 wherein said disorder is cerebral infarction, cerebral embolism or subarachidonic hemorrhage. .Iaddend..Iadd.41. A method according to claim 37 wherein said effective amount is from about 1 to about 100 mg of said compound and is orally administered 1 to 3 times/day. .Iaddend..Iadd.42. A method according to claim 37 wherein said effective amount is from about 0.01 to about 10 mg of said compound and is intravenously administered 2 to 5 times/day. .Iaddend..Iadd.43. A method according to claim 37 wherein said effective amount is administered continuously by instillation. .Iaddend..Iadd.44. A method according to claim 37 wherein said effective amount is from about 1 to about 100 mg of said compound and is intrarectally administered 1 to 3 times/day. .Iaddend..Iadd.45. A method for providing a therapeutic action comprising administering an effective amount of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for the treatment of trauma in mammals. .Iaddend..Iadd.46. A method for providing a therapeutic action comprising administering an effective amount of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for mammals during the emergence from anesthesia. .Iaddend..Iadd.47. A method for providing a therapeutic action comprising administering an effective amount of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for the prevention of recurrence of cerebrovascular disorders in mammals. .Iaddend..Iadd.48. A method for providing a prophylactic and therapeutic action comprising administering an effective amount of pyrazolone derivative to provide a prophylactic and therapeutic action for cerebral, cardiac or peripheral circulatory disorders in mammals, said derivative having the formula: ##STR63##.Iaddend.wherein R 1  represents a hydrogen atom, an aryl group, an alkyl group having 1 to 5 carbon atoms; R 2  represents a hydrogen atom, an aryloxy group, an alkyl group having 1 to 5 carbon atoms; or R 1  and R 2  taken together represent an alkylene group having 3 to 5 carbon atoms; R 3  represents a cycloalkyl group having 5 to 7 carbon atoms, a naphthyl group, or a phenyl group which is unsubstituted or para or meta substituted with 1 to 3 substituents which are the same or different selected from the group consisting of alkyl groups having 1 to 5 carbon atoms, alkoxy groups having 1 to 5 carbon atoms, alkoxycarbonyl groups having a total carbon number of 2 to 5, alkylmercapto groups having 1 to 3 carbon atoms, halogen atoms, a trifluoromethyl group, a carboxyl group, a cyano group, a hydroxyl group, a nitro group or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier. 
     
     
        .Iadd.49.  A method according to claim 48 wherein said disorder is accompanied by an ischemic disease. .Iaddend..Iadd.50. A method according to claim 49 wherein said circulatory disorder said disorder is a peripheral circulatory disorder. .Iaddend..Iadd.51. A method according to claim 48 wherein said cardiac disorder is myocardial ischemia or angina pectoris. .Iaddend..Iadd.52. A method according to claim 48 wherein said cerebral disorder is a cerebrovascular disorder or a lowering in cerebral functions. .Iaddend..Iadd.53. A method according to claim 48 wherein said cerebral disorder is selected from the group consisting of cerebral apoplexy, cerebral infarction, ischemic cerebrovascular disorders, subarachnoidic hemorrhage, intracerebral hemorrhage, cerebral embolism, cerebral edema, trauma, vascular dementia, cerebrovascular tissue lesion, cerebral arteriosclerosis and obnubilation. .Iaddend..Iadd.54. A method according to claim 48 wherein the aryl group represented by R 1  is a phenyl group or phenyl groups which are substituted with a methyl group, a butyl group, a methoxy group, a butoxy group, a hydroxyl group or a chlorine atom; the alkyl group having 1 to 5 carbon atoms represented by R 1  or R 2  is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group or a pentyl group; the aryloxy group represented by R 2  is a phenoxy group, a p-methylphenoxy group, a p-methoxyphenoxy group, a p-chlorophenoxy group or a p-hydroxyphenoxy group; the cycloalkyl group having 5 to 7 carbon atoms represented by R 3  is a cyclopentyl group, a cyclohexyl group or a cycloheptyl group; as the substituent for the phenyl group in the definition of R 3 , the alkoxy group having 1 to 5 carbon atoms is a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group or a pentyloxy group; the alkoxycarbonyl group having a total carbon number of 2 to 5 is a methoxycarbonyl group, an ethyoxycarbonyl group, a propoxycarbonyl group or a butoxycarbonyl group; the alkylmercapto group having 1 to 3 carbon atoms is a methylmercapto group, an ethylmercapto group or a propylmercapto group. .Iaddend..Iadd.55. A method according to claim 48 wherein said pyrazolone derivative is selected from the group consisting of: 3-Methyl-1-phenyl-2-pyrazolin-5-one;   3-Methyl-1-(4-methylphenyl)-2-pyrazolin-5-one;   1-(4-Methoxyphenyl)-3-methyl-2-pyrazolin-5-one;   1-(4-Ethoxyphenyl)-3-methyl-2-pyrazolin-5-one;   1-(4-Chlorophenyl)-3-methyl-2-pyrazolin-5-one;   1-Phenyl-3-propyl-3-pyrazolin-5-one;   3,4-Dimethyl-1-phenyl-2-pyrazolin-5-one;   4-Isobutyl-3-methyl-1-phenyl-2-pyrazolin-5-one;   3,3a,4,5,6,7-Hexahydro-2-phenyl-2H-indazol-3-one; and   1-Cyclohexyl-3-methyl-2-pyrazolin-5-one; or a pharmaceutically acceptable salt thereof. .Iaddend..Iadd.56. A method according to claim 48 wherein said composition is useful as an inhibitor against lipid peroxidation. .Iaddend..Iadd.57. A method according to claim 48 wherein 3 methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof is useful as an agent for normalizing cerebral     
     
     
        functions. .Iaddend..Iadd.58.  A pharmaceutical composition comprising 0.01-100 mg of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for cerebral, cardiac or peripheral circulatory disorders in mammals. .Iaddend..Iadd.59. A pharmaceutical composition according to claim 58, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for myocardial infarction or cardiac insufficiency. .Iaddend..Iadd.60. A pharmaceutical composition according to claim 58, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for cerebral ischemia. .Iaddend..Iadd.61. A pharmaceutical composition according to claim 58, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for cerebral infarction, cerebral embolism or subarachnoidic hemorrhage. .Iaddend..Iadd.62. A pharmaceutical composition comprising 0.01-100 mg of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for the treatment of trauma in mammals. .Iaddend..Iadd.63. A pharmaceutical composition comprising 0.01-100 mg of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for the prevention of the recurrence of cerebrovascular disorders in mammals. 
     
     
        .Iaddend..Iadd.64.  A pharmaceutical composition comprising 0.01-100 mg of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof in a pharmaceutical carrier to provide a therapeutic action for 
     
     
        mammals during the emergence from anesthesia. .Iaddend..Iadd.65.  A pharmaceutical composition comprising 0.01-100 mg of a pyrazolone derivative to provide a prophylactic and therapeutic action for cerebral, cardiac or peripheral circulatory disorders in mammals, said derivative having the formula: ##STR64## wherein R 1  represents a hydrogen atom, an aryl group, an alkyl group having 1 to 5 carbon atoms; R 2  represents a hydrogen atom, an aryloxy group, an alkyl group having 1 to 5 carbon atoms; or R 1  and R 2  taken together represent an alkylene group having 3 to 5 carbon atoms; R 3  represents a cycloalkyl group having 5 to 7 carbon atoms, a naphthyl group, or a phenyl group which is unsubstituted or para or meta substituted with 1 to 3 substituents which are the same or different selected from the group consisting of alkyl groups having 1 to 5 carbon atoms, alkoxy groups having 1 to 5 carbon atoms, alkoxycarbonyl groups having a total carbon number of 2 to 5, alkylmercapto groups having 1 to 3 carbon atoms, halogen atoms, a trifluoromethyl group, a carboxyl group, a cyano group, a hydroxyl group, and a nitro group; or a pharmaceutically 
     
     
        acceptable salt thereof in a pharmaceutical carrier. .Iaddend..Iadd.66.  A pharmaceutical composition in accordance with claim 65, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for cerebral, cardiac or peripheral circulatory disorders accompanied by an ischemic disease. .Iaddend..Iadd.67. A pharmaceutical composition in accordance with claim 65, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for a peripheral circulatory disorder accompanied by an ischemic disease. .Iaddend..Iadd.68. A pharmaceutical composition in accordance with claim 65, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for myocardial ischemia or angina pectoris accompanied by an ischemic disease. .Iaddend..Iadd.69. A pharmaceutical composition in accordance with claim 65, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for a cerebrovascular disorder or a lowering in cerebral functions accompanied by an ischemic disease. .Iaddend..Iadd.70. A pharmaceutical composition in accordance with claim 58 or 65, said composition comprising an effective amount of the pyrazolone to provide a prophylactic and therapeutic action for a disorder selected from the group consisting of cerebral apoplexy, cerebral infarction, ischemic cerebrovascular disorders, subarachnoidic hemorrhage, intracerebral hemorrhage, cerebral embolism, cerebral edema, trauma, vascular dementia, cerebrovascular tissue lesion, cerebral arteriosclerosis and obnubilation. .Iaddend..Iadd.71. A pharmaceutical composition in accordance with claim 65 wherein the aryl group represented by R 1  is a phenyl group or phenyl groups which are substituted with a methyl group, a butyl group, a methoxy group, a butoxy group, a hydroxyl group or a chlorine atom; the alkyl group having 1 to 5 carbon atoms represented by R 1  or R 2  is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group or a pentyl group; the aryloxy group represented by R 2  is a phenoxy group, a p-methylphenoxy group, a p-methoxyphenoxy group, a p-chlorophenoxy group or a p-hydroxyphenoxy group; the cycloalkyl group having 5 to 7 carbon atoms represented by R 3  is a cyclopentyl group, a cyclohexyl group or a cycloheptyl group; as the substituent for the phenyl group in the definition of R 3 , the alkoxy group having 1 to 5 carbon atoms is a methyl group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group or a pentyloxy group; the alkoxycarbonyl gross having a total carbon number of 2 to 5 is a methoxycarbonyl group, an ethyoxycarbonyl group, a propoxycarbonyl group or a butoxycarbonyl group; the alkylmercapto group having 1 to 3 carbon atoms is a methylmercapto group, an ethylmercapto group or a propylmercapto group. .Iaddend..Iadd.72. A pharmaceutical composition in accordance with claim 65 wherein said pyrazolone derivative is selected from the group consisting of: 3-Methyl-1-phenyl-2-pyrazolin-5-one;   3-Methyl-1-(4-methylphenyl)-2-pyrazolin-5-one;   1-(4-Methoxyphenyl)-3-methyl-2-pyrazolin-5-one;   1-(4-Ethoxyphenyl)-3-methyl-2-pyrazolin-5-one;   1-(4-Chlorophenyl)-3-methyl-2-pyrazolin-5-one;   1-Phenyl-3-propyl-3-pyazolin-5-one;   3,4-Dimethyl-1-phenyl-2-pyrazolin-5-one;   4-Isobutyl-3-methyl-1-phenyl-2-pyrazolin-5-one;   3,3a,4,5,6,7-Hexahydro-2-phenyl-2H-indazol-3-one; and   1-Cyclohexyl-3-methyl-2-pyrazolin-5-one;   
     
     
       or a pharmaceutically acceptable salt thereof. .Iaddend..Iadd.73.  A pharmaceutical composition in accordance with claim 65, said composition comprising an effective amount of the pyrazolone to act as an inhibitor against lipid peroxidation. .Iaddend..Iadd.74. A pharmaceutical composition in accordance with claim 65, said composition comprising an effective amount of 3-methyl-1-phenyl-2-pyrazolin-5-one or a pharmaceutically acceptable salt thereof to act as an agent for normalizing cerebral functions. .Iaddend.