Modafinil modulates GABA-activated currents in rat hippocampal pyramidal neurons.

Modafinil is a well-known psychoactive drug used to treat narcolepsy, hypoglycemia, cerebral ischemia and Parkinson's disease. Previous studies showed that ATP-sensitive potassium channels (K(ATP)) play a key role in response to cerebral ischemia, hypoglycemia or metabolic inhibition. Modafinil (0.01-1 mM) dose-dependently decreased the GABA-activated currents (I(GABA)). Pretreatment with the K(ATP) channel blocker, glibenclamide (10 microM), significantly reduced the decrease of I(GABA) caused by modafinil. Thus, the inhibitory effect of modafinil on the I(GABA) is indirect by modulating K(ATP) channel activation, at least in part mediated by K(ATP) channel.