Mephenytoin, (+)- is an (S)-enantiomer of anticonvulsant drug mephenytoin. Mephenytoin is usually administrated as a 1:1 racemic mixture of the (R)- and (S)-enantiomers. The marked stereoselectivity of 4’-hydroxylation of the phenyl ring of S-mephenytoin together with the relatively slow N-demethylation to R-PEH (R-5-phenyl-5-ethylhydantom) and even slower renal clearance results in a dramatic difference in the pharmacokinetic disposition of the S- and R-enantiomers of mephenytoin in man. As a consequence, S-mephenytoin provides a negligible contribution to circulating hydantoins, whereas R-mephenytoin is converted to the pharmacologically active demethylated product R-PEH which is the major circulating hydantoin during chronic administration of the racemic drug. Only the 4’-hydroxylation of the (S)-mephenytoin is absent in patents who are poor metabolizers of mephenytoin. It is not clear as to the clinical consequences of the accumulation of (S)-mephenytoin for the poor metabolizer phenotype. Indeed, it may be the extensive metabolizer who is at great risk of adverse effects by the formation of potentially toxic oxidative metabolites of (S)-mephenytoin.

Mephenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, mephenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of posttetanic potentiation at synapses. Loss of posttetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Mephenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. The mechanism of action of mephenytoin is not definitely known, but extensive research strongly suggests that its main mechanism is to block frequency-, use- and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials. Mephenytoin is no longer available in the US or the UK. It is still studied largely because of its interesting hydroxylation polymorphism.

Mephenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, mephenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of posttetanic potentiation at synapses. Loss of posttetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Mephenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. The mechanism of action of mephenytoin is not definitely known, but extensive research strongly suggests that its main mechanism is to block frequency-, use- and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials. Mephenytoin is no longer available in the US or the UK. It is still studied largely because of its interesting hydroxylation polymorphism.