Allergan, Inc.

Allergan Sales, Inc.

Joseph S Adorante

George R Ehring

Larry Allen Wheeler

Thomas C Malone

Elizabeth WoldeMussie

Guadalupe Ruiz

John E Donello

Scott M Whitcup

Michael E Garst

Lloyd Jay Dolby

Shervin Esfandiari

Mark R Hansen

Alfred Arthur Avey, Jr

Jeremiah Marsden

Vivian Rose MacKenzie

David Charles Muchmore

Herman Ng

Hau Ton

Kara L Kopper

Jia Chian Li

Howard B Rind

Ellen Chao

Michael S Garst

Alison M Moore

The present invention is directed to a compound of Formula I or a pharmaceutically acceptable salt thereof; wherein R, R, R, R, R, 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.

Benzimidazole derivatives as selective blockers of persistent sodium current

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.

Treating pain using selective antagonists of persistent sodium current

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.

Treating neurological disorders using selective antagonists of persistent sodium current

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

High-throughput screen for identifying selective persistent sodium channels channel blockers

A method for identifying a selective persistent Nachannel blocker by measuring the ability of the blocker to reduce or inhibit a persistent Nacurrent to a greater degree than a transient Nacurrent. Aspects of the present method provide Nadepletion/repletion methods for identifying a selective blocker of a persistent Nachannel, 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 Nachannel.

A method for identifying a Nachannel blocker, including providing a cell containing a Nachannel, demonstrating both a transient and a persistent current. The cell includes a potassium (K) channel and a Na/K ATPase (Napump). 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 Nachannel 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 Nachannel blocker. Thereafter, a change in cell membrane potential is optically measured.

High-throughput screen for identifying channel blockers that selectively distinguish transient from persistent sodium channels

A method for preventing retinal ganglion cell depth, associated with glaucoma, 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.

Targeting the reverse mode of the Na&plus;/Ca2&plus; exchanger for the treatment of optic neuropathy associated with glaucoma and ischemic optic neuropathy

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Irvine, CA, United States of America

Joseph S Adorante