Effects of ethosuximide and tetramethylsuccinimide on cultured cortical neurons

In cultured cortical neurons, ethosuximide (ESM) had unexpected actions for an antiepileptic drug; it slightly diminished the effects of inhibitory neurotransmitters, GABA, and glycine. ESM had no direct membrane effects, did not change action potential characteristics or alter spontaneous activity, and did not reverse the effects of convulsants that are GABA antagonists. The structurally related convulsant tetramethylsuccinimide (TMSM) reduced the amplitude of GABA-mediated inhibitory postsynaptic potentials and antagonized responses to applied GABA, effects not reversed by ESM. The convulsant effects of TMSM include a blockade of postsynaptic GABA actions, but the antiepileptic effects of ESM are not due to an enhancement of GABA-mediated inhibition.