Glutamate receptor antagonists and methods of use
The present invention relates to methods and compositions for modulating platelet activity by inhibiting or activating glutamate receptors. The invention further relates to preventing or treating thrombotic diseases.
1. A method of delaying thrombus formation in a subject comprising:
administering to the subject an effective amount of a compound that inhibits the activity of one or more glutamate receptors in non-neuronal cells, thereby delaying thrombus formation in a subject wherein the compound is selected from the group consisting of CNQX, NBQX, GYKI52466, GYKI53655, GYKI47261, cyclothiazide, YM90K, Zonampel (YM872), YM928, Perampanel (E2007), CP-465,022, ZK200775, Talampanel (LY300164), and Tezampanel (NGX424), LY382884, NS-102, UBP301, CX-516, CX-717, and philanthotoxin-343, and pharmaceutically acceptable salts, prodrugs, esters, and hydrates thereof.
2. The method of claim 1 , wherein the method delays platelet activation, aggregation, adherence, clotting, or thrombosis.
3. The method of claim 1 , wherein the AMPAR comprises at least one subunit selected from the group consisting of: GluR1, GluR2, GluR3 and GluR4.
4. A method of treating thrombosis in a subject comprising: administering to the subject an effective amount of a compound that inhibits the activity of AMPA receptors in non-neuronal cells in a subject, thereby treating thrombosis in the subject, wherein the compound is selected from the group consisting of CNQX, NBQX, GYK152466, GYK153655, GYK147261, cyclothiazide, YM90K, Zonampel (YM872), YM928, Perampanel (E2007), CP-465.022, ZK200775, Talampanel (LY300164), Tezampanel (NGX424), LY382884, NS-102, UBP301, CX-516, CX-717, and philanthotoxin-343, and pharmaceutically acceptable salts, prodrugs, esters, and hydrates thereof.
5. A method of delaying clot formation or progression in a subject comprising: administering to the subject an effective amount of a compound that inhibits the activity of AMPA receptors in platelet cells in a subject, thereby delaying clot formation or progression wherein the compound is selected from the group consisting of CNQX, NBQX, GYKI52466, GYKI53655, GYKI47261, cyclothiazide, YM90K, Zonampel (YM872), YM928, Perampanel (E2007), CP-465,022, ZK200775, Talampanel (LY300164), and Tezampanel (NGX424), LY382884, NS-102, UBP301, CX-516, CX-717, and philanthotoxin-343, and pharmaceutically acceptable salts, prodrugs, esters, and hydrates thereof.
6. A method of treating a thrombotic disease or disorder in a subject comprising: administering to the subject an effective amount of a compound that inhibits the activity of AMPA receptors in platelet cells in a subject and delays thrombus formation, thereby treating or preventing a thrombotic disease or disorder in a subject wherein the compound is selected from the group consisting of CNQX, NBQX, GYKI52466, GYKI53655, GYKI47261, cyclothiazide, YM90K, Zonampel (YM872), YM928, Perampanel (E2007), CP-465,022, ZK200775, Talampanel (LY300164), and Tezampanel (NGX424), LY382884, NS-102, UBP301, CX-516, CX-717, and philanthotoxin-343, and pharmaceutically acceptable salts, prodrugs, esters, and hydrates thereof.