Epileptic activity can be induced acutely by blocking synaptic and voltage-gated inhibitory conductances or by activating synaptic and voltage-gated excitatory conductances. Seizures are blocked by the opposite manipulations: increasing inhibition or decreasing excitation. Several decades of these types of pharmacological experiments have established the idea that an imbalance between inhibitory and excitatory conductances leads to seizures (i.e., is ictogenic) in otherwise normal brain tissue.This imbalance is most clearly embodied clinically in toxic exposures such as domoic acid, which activates excitatory GluK1 glutamate receptors, or by overdoses of theophylline, which blocks the inhibitory adenosine A1 receptor.

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