Retigabine is the first and only anti-epileptic drug previously approved by FDA in 2011. However, long-term medication of retigabine leads to serious dose-related side-effects on some patients, such as skin and retinal pigmentation. Thus it received a black box warning in 2013, and was discontinued from all markets in 2017 for commercial reasons.

NAN’s and GAO’s groups have spent eight years on developing pynegabine as the anti-epileptic drug candidate. They have made several rounds of structural optimization considering pharmacodynamic safety and metabolic characteristics. With targeting KCNQ potassium channel, pynegabine has obtained fully independent intellectual property rights.

Preclinical studies showed that pynegabine improves upon chemical stability and brain distribution over retigabine, and it not only reduces the risk of pigmentation but also shows greater potency than retigabine in multiple animal models including refractory epilepsy model.

Pynegabine, hopefully, will become a new anti-epileptic drug of Best/Only in-class KCNQ modulator with proprietary intellectual property rights and following further clinical trials. It may provide new drug treatment options for refractory epilepsy patients in the future.

The study was also supported by researchers from Center for Drug Metabolism and Pharmacokinetics Research of SIMM, Center for Pharmaceutical Analysis and Solid-state Chemistry Research of SIMM, Center for pharmaceutics Research of SIMM, Zhejiang University Center for Drug Safety Evaluation and Research, and National Shanghai Center for New Drug Safety Evaluation and Research.