indication

For the control of absence (petit mal) seizures that are refractory to other drugs.

pharmacology

Used in the treatment of epilepsy. Methsuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli.

mechanism of action

Binds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.

toxicity

Acute overdoses may produce nausea, vomiting, and CNS depression including coma with respiratory depression. Levels greater than 40 µg/mL have caused toxicity and coma has been seen at levels of 150 µg/mL.

half life

1.4-2.6 hours for mesuximide and 28-38 hours for the active metabolite.

drug interactions

Lamotrigine: Methsuximide decreases the effect of lamotrigine

Ticlopidine: Ticlopidine may decrease the metabolism and clearance of Methsuximide. Consider alternate therapy or monitor for adverse/toxic effects of Methsuximide if Ticlopidine is initiated, discontinued or dose changed.

Triprolidine: The CNS depressants, Triprolidine and Methsuximide, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.