Effects of different classes of antiepileptic drugs on brain-stem pathways

Antiepileptic drugs probably act by preventing the spread of the abnormal paroxysmal activity from the epileptogenic focus to surrounding normal neurons. An investigation of the mechanism of action of established anticonvulsant drugs on normal neuronal systems may therefore offer useful insights into the pathogenesis of the seizure disorders that these drugs serve to control. Antiabsence drugs (ethosuximide, valproate) depress reticular inhibitory pathways. Drugs effective against generalized tonic-clonic seizures (phenytoin, carbamazepine, valproate) depress reticular excitatory pathways. Drugs that are also effective against trigeminal neuralgia (phenytoin, carbamazepine) also depress afferent excitation and facilitate segmental inhibition in the trigeminal complex. Drugs that depress afferent excitation and facilitate segmental inhibition but do not depress the reticular system (baclofen) are effective against trigeminal neuralgia but do not have clinical antiepileptic properties. These observations indicate that the ability to depress the reticular core is an important characteristic of antiepileptic drugs, and suggest that the reticular core is involved in the spread and generalization of clinical seizures.