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Targeting Ischemic Stroke with a Novel Opener of ATP-Sensitive Potassium Channels in the Brain

Department of Cardiovascular Pharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, People's Republic of China (H.W., Y.Z., H.-S.F.); Pharmacology Department, Nanjing Medical University, Nanjing People's Republic of China (X.C.T., G.H.); and Thadweik Academy of Medicine, Beijing, People's Republic of China (X.C.T.)

During cerebral ischemia, the opening of neuronal ATP-sensitive potassium channels (K_ATP channels) affords intrinsic protection by regulating membrane potential. To augment this endogenous mechanism, we have synthesized iptakalim, a K_ATP opener. Through K_ATP channel activation, iptakalim affected multiple pathways of the glutamatergic system, limiting glutamate release and receptor actions, which are involved in excitotoxicity during ischemic damage. The molecule readily penetrated the brain and showed low toxicity in animal experiments. In different animal models of stroke as well as in cell cultures, iptakalim provided significant neuroprotection, not only in promoting behavioral recovery but also in protecting neurons against necrosis and apoptosis. This compound thus has promise as a neuroprotective drug for the treatment of stroke and other forms of neuronal damage.

Address correspondence to: Hai Wang, Department of Cardiovascular Pharmacology, Beijing Institue of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, P.R.China. E-mail: wh9588{at}yahoo.com.cn

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