Agents for preventing and/or treating higher brain dysfunctions
(wherein R 1 , R 2 and R 3 are the same or different, and represent a hydrogen atom, lower alkyl, lower alkenyl or lower alkynyl; R 4 represents cycloalkyl, —(CH 2 ) n —R 5 or a group represented by the above formula (II); and X 1 and X 2 are the same or different, and represent an oxygen atom or a sulfur atom) The present invention provides, for example, agents for preventing and/or treating higher brain dysfunction comprising, as an active ingredient, a xanthine derivative represented by the above formula (I) or a pharmaceutically acceptable salt thereof.
1 . A pharmaceutical composition comprising, as an active ingredient, a xanthine derivative represented by formula (I):
[wherein
R 1 , R 2 and R 3 independently represent a hydrogen atom, lower alkyl, lower alkenyl or lower alkynyl;
R 4 represents cycloalkyl, —(CH 2 ) n —R 5 (wherein R 5 represents substituted or unsubstituted aryl, or substituted or a unsubstituted heterocyclic group; and n represents an integer of 0 to 4) or a group represented by formula (II):
(wherein Y 1 and Y 2 independently represent a hydrogen atom, halogen or lower alkyl; and Z represents substituted or unsubstituted aryl or a substituted or unsubstituted heterocyclic group);
X 1 and X 2 independently represent an oxygen atom or a sulfur atom]
or a pharmaceutically acceptable salt thereof
together with a pharmaceutically acceptable carrier.
2 . The composition according to claim 1 , wherein X 1 and X 2 each is an oxygen atom.
3 . The composition according to the claim 1 or 2 , wherein R 4 is represented by formula (II):
4 . The composition according to claim 3 , wherein Y 1 and Y 2 are both hydrogen atoms.
5 . The composition according to claim 3 , wherein Z is substituted or unsubstituted aryl or a group represented by formula (III):
(wherein R 6 represents a hydrogen atom, hydroxy, lower alkyl, lower alkoxy, halogen, nitro or amino; and m represents an integer of 1 to 3).
6 . A method for preventing and/or treating a higher brain dysfunction caused by brain injury comprising administering an effective amount of the composition according to claim 1 to a patient in need thereof.
7 . The method according to claim 6 , wherein the brain injury is due to aging.
8 . The method according to claim 6 , wherein the brain injury is due to a disorder selected from the group consisting of head trauma and cerebrovascular accident.
9 . The method according to any one of claims 6 to 8 , wherein the higher brain dysfunction is an impairment of higher brain function selected from the group consisting of memory, thinking, recognition, action and learning.
10 . The method according to any one of claims 6 to 8 , wherein the higher brain dysfunction is selected from the group consisting of agnosia, amnesia and apraxia.
11 . The method according to any one of claims 6 to 8 , wherein the higher brain dysfunction is a memory impairment.
12 . The method according to any one of claims 6 to 8 , wherein the higher brain dysfunction is a learning impairment.
13 . (canceled)
14 . A method of producing a pharmaceutical composition comprising the steps of selecting a xanthine derivative represented by formula (I):
[wherein R 1 , R 2 and R 3 independently represent a hydrogen atom, lower alkyl, lower alkenyl or lower alkynyl;
R 4 represents cycloalkyl, —(CH 2 ) n —R 5 (wherein R 5 represents substituted or unsubstituted aryl, or substituted or a unsubstituted heterocyclic group; and n represents an integer of 0 to 4) or a group represented by formula (II):
(wherein Y 1 and Y 2 independently represent a hydrogen atom, halogen or lower alkyl; and Z represents substituted or unsubstituted aryl or a substituted or unsubstituted heterocyclic group);
X 1 and X 2 independently represent an oxygen atom or a sulfur atom]
or a pharmaceutically acceptable salt thereof; and
admixing said xanthine derivative or pharmaceutically acceptable salt with a pharmaceutically acceptable carrier.
15 . The composition according to claim 4 , wherein Z is substituted or unsubstituted aryl or a group represented by formula (III):
(wherein R 6 represents a hydrogen atom, hydroxy, lower alkyl, lower alkoxy, halogen, nitro or amino; and m represents an integer of 1 to 3).