alpha 2-adrenergic antagonists suppress epileptiform EEG activity in a petit mal seizure model

Experiments were performed to determine the effects of yohimbine, piperoxan, and mianserin on the flash-evoked afterdischarge (FEAD) in rat. All three drugs are alpha-adrenergic antagonists, which block the inhibition of norepinephrine-release mediated by presynaptic (alpha 2) receptors. It was predicted that these drugs would exert dose-dependent biphasic effects on FEAD: at low doses, which act presynaptically, the FEAD would be suppressed; while at higher doses, which also block postsynaptic (alpha 1) receptors, the FEAD would be disinhibited. The dose response curves for yohimbine and piperoxan were, in fact, biphasic with low doses decreasing the amount of FEAD, while higher doses returned the amount of FEAD to baseline. No biphasic effect was seen with mianserin. These observations are consistent with the fact that yohimbine and piperoxan are more potent antagonists at alpha 2- than at alpha 1-receptors, whereas the affinities of mianserin for the two receptor types is comparable. The results of these experiments support the hypothesis that norepinephrine modulates FEAD.