Targeting ischemic stroke with a novel opener of ATP-sensitive potassium channels in the brain.
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.
Department of Cardiovascular Pharmacology, Beijing Institue of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, P.R.China. wh9588@yahoo.com.cn
Hai
H
Wang
Ying-li
YL
Zhang
Xing-Chun
XC
Tang
Hua-Song
HS
Feng
Gang
G
Hu
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000517:prevention & control*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004594:Electrophysiology; D005849:Gerbillinae; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives*; D008565:Membrane Proteins / Q000819:agonists / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D051381:Rats; D020521:Stroke / Q000150:complications / Q000378:metabolism
D008565:Membrane Proteins; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C084257:PC 12 ester; D018698:Glutamic Acid; D005998:Glycine