Mechanism of Action
The drug works by inhibiting the sulfonylurea receptor 1 (SUR1), the regulatory subunit of the ATP-sensitive potassium channels (KATP) in pancreatic beta cells. This inhibition causes cell membrane depolarization opening voltage-dependent calcium channel. This results in an increase in intracellular calcium in the beta cell and subsequent stimulation of insulin release.
After an cerebral ischemic insult the blood brain barrier is broken and glibenclamide can reach the central nervous system. Glibenclamide has been shown to bind more efficiently to the ischemic hemisphere. Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells and by reactive microglia.
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