Abstract: The present invention is directed to a compound of Formula I or a pharmaceutically acceptable salt thereof; wherein R, R1, R2, R3, R4, m, and n are as defined herein, to pharmaceutical compositions comprising said compound, and to methods of treating diseases or conditions mediated by elevated persistent sodium current, such as an ocular disorder, multiple sclerosis, seizure disorder, and chronic pain.

Abstract: The present invention is directed to a compound of Formula I or a pharmaceutically acceptable salt thereof; wherein R, R1, R2, R3, R4, m, and n are as defined herein, to pharmaceutical compositions comprising said compound, and to methods of treating diseases or conditions mediated by elevated persistent sodium current, such as an ocular disorder, multiple sclerosis, seizure disorder, and chronic pain.

Abstract: The present invention is directed to a compound of Formula I or a pharmaceutically acceptable salt thereof; wherein R, R1, R2, R3, R4, m, and n are as defined herein, to pharmaceutical compositions comprising said compound, and to methods of treating diseases or conditions mediated by elevated persistent sodium current, such as an ocular disorder, multiple sclerosis, seizure disorder, and chronic pain.

Abstract: The present invention is directed to a compound of Formula I or a pharmaceutically acceptable salt thereof; wherein R, R1, R2, R3, R4, m, and n are as defined herein, to pharmaceutical compositions comprising said compound, and to methods of treating diseases or conditions mediated by elevated persistent sodium current, such as an ocular disorder, multiple sclerosis, seizure disorder, and chronic pain.

Abstract: The present invention provides methods of treating chronic pain in a mammal by administering to the mammal an effective amount of a selective persistent sodium channel antagonist that has at least 20-fold selectivity for persistent sodium current relative to transient sodium current.

Abstract: The present invention provides methods of treating neurological disorders in a mammal by administering to the mammal an effective amount of a selective persistent sodium channel antagonist that has at least 20-fold selectivity for persistent sodium current relative to transient sodium current.

Abstract: The present invention provides methods of treating chronic pain in a mammal by administering to the mammal an effective amount of a selective persistent sodium channel antagonist that has at least 20-fold selectivity for persistent sodium current relative to transient sodium current.

Abstract: The present invention provides methods of treating chronic pain in a mammal by administering to the mammal an effective amount of a selective persistent sodium channel antagonist that has at least 20-fold selectivity for persistent sodium current relative to transient sodium current.

Abstract: A method for identifying a selective persistent Na+ channel blocker by measuring the ability of the blocker to reduce or inhibit a persistent Na+ current to a greater degree than a transient Na+ current. Aspects of the present method provide Na+ depletion/repletion methods for identifying a selective blocker of a persistent Na+ channel, hyperpolarization methods for identifying a blocker of a persistent Na+ channel, and Na/K ATPase pump inhibitor methods for identifying a selective blocker of a persistent Na+ channel.

Abstract: The present invention provides methods of treating neurological disorders in a mammal by administering to the mammal an effective amount of a selective persistent sodium channel antagonist that has at least 20-fold selectivity for persistent sodium current relative to transient sodium current.

Abstract: A method for identifying a selective persistent Na+ channel blocker by measuring the ability of the blocker to reduce or inhibit a persistent Na+ current to a greater degree than a transient Na+ current. Aspects of the present method provide Na+ depletion/repletion methods for identifying a selective blocker of a persistent Na+ channel, hyperpolarization methods for identifying a blocker of a persistent Na+ channel, and Na/K ATPase pump inhibitor methods for identifying a selective blocker of a persistent Na+ channel.

Abstract: The present invention provides methods of treating neurological disorders in a mammal by administering to the mammal an effective amount of a selective persistent sodium channel antagonist that has at least 20-fold selectivity for persistent sodium current relative to transient sodium current.

Abstract: A method for identifying a selective persistent Na+ channel blocker by measuring the ability of the blocker to reduce or inhibit a persistent Na+ current to a greater degree than a transient Na+ current. Aspects of the present method provide Na+ depletion/repletion methods for identifying a selective blocker of a persistent Na+ channel, hyperpolarization methods for identifying a blocker of a persistent Na+ channel, and Na/K ATPase pump inhibitor methods for identifying a selective blocker of a persistent Na+ channel.

Abstract: A method for identifying a selective persistent Na+ channel blocker by measuring the ability of the blocker to reduce or inhibit a persistent Na+ current to a greater degree than a transient Na+ current. Aspects of the present method provide Na+ depletion/repletion methods for identifying a selective blocker of a persistent Na+ channel, hyperpolarization methods for identifying a blocker of a persistent Na+ channel, and Na/K ATPase pump inhibitor methods for identifying a selective blocker of a persistent Na+ channel.

Abstract: A method for treating a neurodegenerative condition, in an animal of the mammalian species, including humans, comprising the step of administering to ganglion cells and their axons (optic nerve) of said mammal a pharmaceutical composition which comprises as its active ingredient one or more compounds having activity for blocking a reverse mode of the sodium/calcium exchanger.

Abstract: A method for identifying a selective persistent Na+ channel blocker by measuring the ability of the blocker to reduce or inhibit a persistent Na+ current to a greater degree than a transient Na+ current. Aspects of the present method provide Na+ depletion/repletion methods for identifying a selective blocker of a persistent Na+ channel, hyperpolarization methods for identifying a blocker of a persistent Na+ channel, and Na/K ATPase pump inhibitor methods for identifying a selective blocker of a persistent Na+ channel.

Abstract: The present invention provides methods of treating chronic pain in a mammal by administering to the mammal an effective amount of a selective persistent sodium channel antagonist that has at least 20-fold selectivity for persistent sodium current relative to transient sodium current.

Abstract: The present invention provides methods of treating neurological disorders in a mammal by administering to the mammal an effective amount of a selective persistent sodium channel antagonist that has at least 20-fold selectivity for persistent sodium current relative to transient sodium current.

Abstract: A method for identifying a Na+ channel blocker, including providing a cell containing a Na+ channel, demonstrating both a transient and a persistent current. The cell includes a potassium (K+) channel and a Na/K ATPase (Na+ pump). A fluorescent dye is disposed into the well. The fluorescent dye is sensitive to change in cell membrane potential in order to enable optical measurement of cell membrane potential. A Na+ channel blocker, to be identified, is added to the well and a stimulating current is passed through the cell in an amount sufficient to generate an action potential before and after the addition of the Na+ channel blocker. Thereafter, a change in cell membrane potential is optically measured.

Abstract: A method and composition for altering a plausible sequence of pathological events in retinal ganglion cells associated with glaucoma, the sequence including membrane depolarization, influx of millimolar amounts of Na+ via non-inactivating Na+ channels, and the lethal elevation of cell Ca2+ due to reversal of the Na+/Ca2+ exchanger. The method includes blocking, by administration of a selected composition, of associated, non-inactivating Na+ channels in retinal ganglion cells in order to limit Na+/Ca+ exchange in the retinal ganglion cells and prevent buildup of the Ca2+ level in the retinal ganglion cells to a lethal level. The results in a method of preventing retinal ganglion cell death, associated with glaucoma, by administering to the optic nerve of a mammal, a compound which blocks the non-inactivating sodium ion channels of the optic nerve.