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Updated: Jun 17, 2026

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Novel KCNQ2/Q3 agonists as potential therapeutics for epilepsy and neuropathic pain
Paul C Fritch1, Grant McNaughton-Smith, George S Amato
1Icagen, Inc., Suite 390, 4222 Emperor Boulevard, Durham, North Carolina 27703, USA. pfritch@icagen.com
Abstract:
Current drugs for the treatment of seizure disorders, although effective in many patients, still suffer from a number of failures and are not effective in some forms of resistant epilepsies. Historically, many of these drugs have multiple mechanisms of action including calcium and sodium channel blockade as well as GABAergic activity and thus a number of associated side effects. Modulation of the M-current through opening of KCNQ channels has been proposed as a way to attenuate neuroexcitability and have a therapeutic benefit for the treatment of seizure disorders. Therefore, as part of our program to identify new treatments for epilepsy, we set out to identify agonists of KCNQ channels. High throughput screening of our corporate collection led to the identification of 1, adamantane-1-carboxylic acid (3-methyl-3H-benzothiazol-2-ylidine) hydrazide, a potent KCNQ2/Q3 agonist. Herein, we describe the syntheses and structure-activity relationships of analogues of 1 as well as their in vivo activity in animal models of epilepsy and neuropathic pain.
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