Mglu receptors antagonists for treating disorders associated with mglu receptors including addiction and depression
AssigneeThe Scripps Research Institute
InventorsAthina Markou, Paul Kenny, Neil Paterson, Svetlana Semenova
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Abstract
Methods are provided for treating disorders associated with mGlu receptors by simultaneously inhibiting at least two mGIuRs belonging to at least two different groups. In one embodiment, there are provided methods for treating a disorder associated with MGlu receptors 2, 3, and 5, including administering to a subject in need thereof an effective amount of at least one antagonist which modulates mGIuR2, mGIuR3, and mGIuRS. The disorders treated by the method include, for example, nicotine addiction, cocaine addiction, and depression.
Claims31
A method for treating a metabotropic glutamate disorder, comprising administering to a subject in need thereof, an effective amount of at least one antagonist which modulates metabotropic glutamate receptor 2, metabotropic glutamate receptor 3, and metabotropic glutamate receptor 5, thereby treating the disorder.
A method for treating a metabotropic glutamate disorder, comprising administering to a subject in need thereof, an effective amount of at least one antagonist which modulates metabotropic glutamate receptor 2, and metabotropic glutamate receptor 5, thereby treating the disorder.
A method for treating a metabotropic glutamate disorder, comprising administering to a subject in need thereof an effective amount of at least one antagonist which modulates metabotropic glutamate receptor 3 and metabotropic glutamate receptor 5, thereby treating the disorder.
A combination comprising (a) at least one active ingredient selected from a metabotropic glutamate receptor 2 antagonist and a metabotropic glutamate receptor 3 antagonist, and (b) at least one metabotropic glutamate receptor 5 antagonist, in which the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt, and optionally at least one pharmaceutically acceptable carrier;
- for simultaneous, separate or sequential use.
A combination comprising (a) at least one active ingredient which exhibits antagonistic activity against the metabotropic glutamate receptor 2 and the metabotropic glutamate receptor 3, and (b) at least one metabotropic glutamate receptor 5 antagonist, in which the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt, and optionally at least one pharmaceutically acceptable carrier;
- for simultaneous, separate or sequential use.
A combination comprising (a) at least one metabotropic glutamate receptor 2 antagonist, and (b) at least one active ingredient which exhibits antagonistic activity against the metabotropic glutamate receptor 3 and the metabotropic glutamate receptor 5, in which the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt, and optionally at least one pharmaceutically acceptable carrier for simultaneous, separate or sequential use.
A combination comprising (a) at least one metabotropic glutamate receptor 3 antagonist, and (b) at least one active ingredient which exhibits antagonistic activity against the metabotropic glutamate receptor 2 and the metabotropic glutamate receptor 5, in which the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt, and optionally at least one pharmaceutically acceptable carrier;
- for simultaneous, separate or sequential use.
A method of screening for an agent that improves the ability of a known inhibitor to at least partially normalize an intracranial self-stimulation (ICSS) threshold of a non-human mammalian subject, comprising:
- a) affecting the ICSS threshold of the subject;
- b) administering to the subject, a sufficient amount of the known inhibitor to at least partially normalize the ICSS threshold when administered alone or in combination with another inhibitor, wherein the known inhibitor is an antagonist of at least one of mGluR2, mGluR3, and mGluR5;
- c) administering to the non-human mammalian subject, an effective amount of a test agent, wherein the test agent is a known or suspected antagonist of at least one of mGluR2,mGluR3, and mGluR5;
- and
- d) determining whether the test agent improves the ability of the known inhibitor to at least partially normalize the ICSS threshold, thereby identifying an agent that improves the ability of the known inhibitor to at least partially normalize ICSS threshold.
A method for treating an addictive disorder, comprising:
- a) administering to a subject in need thereof, an effective amount of at least one antagonist that modulates at least one of mGluR2, 3, and 5 during a first time period, wherein the first time period is a time period wherein the subject expects to be in an environment wherein, or exposed to stimuli in the presence of which, the subject habitually uses an addictive substance;
- and
- b) administering at least one antagonist that modulates at least one of mGluR2 and/or 3 during a second time period, wherein the second time period is a time period wherein the subject is suffering from withdrawal and/or depression.
A method for treating depressive symptoms and anxiety symptoms of depression, comprising administering to a subject in need thereof, an effective amount of at least one antagonist which modulates metabotropic glutamate receptor 2, metabotropic glutamate receptor 3, and metabotropic glutamate receptor 5, thereby treating the depressive symptoms and anxiety symptoms of depression.
Dependencies are inferred from the claim text.