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First published on August 10, 2004; DOI: 10.1124/mol.104.003178

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Received for publication June 1, 2004.
Revised August 4, 2004.
Accepted for publication August 4, 2004.

Targeting ischaemic stroke with a novel opener of ATP-sensitive potassium channels in the brain

hai wang 1*, yingli zhang 2, xingchun tang 3, huasong feng 4, hu gang 5

1 Pharmacology and Toxicology 2 pharmacology and toxicology 3 pharmacology 4 pharmaocology and toxicology 5 pharmaocology

* Address correspondence to: E-mail: wh9588{at}yahoo.com.cn

Abstract

During cerebral ischaemia, the opening of neuronal ATP-sensitive potassium channels (KATP channels) affords intrinsic protection by regulating membrane potential. To augment this endogenous mechanism, we have synthesized a KATP opener, iptakalim. Through KATP channel activation, iptakalim affected multiple pathways of the glutamatergic system, limiting glutamate release and receptor actions, which are involved in excitotoxicity during ischaemic 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.


Key words: Glutamate, Ion channel regulation, Potassium, Ischemia/Reperfusion




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