Differential effect of ethosuximide and of electrical stimulation on inhibitory and excitatory mechanisms

Much longer trains of conditioning stimuli are required to elicit inhibition descending from the reticular formation than to elicit segmental inhibition in the trigeminal nucleus. In contrast, a single conditioning stimulus is the most effective in eliciting descending facilitation, while the test stimulus alone is most effective in eliciting segmental excitation. Ethosuximide (ESM) selectively depresses descending inhibition and to a lesser extent segmental inhibition. Thus, ESM only depresses pathways requiring repetitive stimulation, such as inhibitory pathways in the reticular formation. This action would account for ESM's specificity for absence seizures, which are probably due to paroxysmal activity in inhibitory pathways.