TYPES OF
ELECTRICAL DISCHARGES IN GENERALIZED SEIZURES AND SITES OF ACTION OF
ANTISEIZURE MEDICATIONS
Illustrations of types of
electrical discharges in generalized seizures and the sites of action for
antiseizure medications that reduce
excitability or that enhance inhibition.
A. Paroxysmal depolarization shift (PDS) is a
cellular marker of epilepsy and consists of a large depolarization of a group
of neurons with action potentials,
as indicated by the vertical lines on the large depolarization. The PDS is
followed by repolarization. The PDS and repolarization corresponds to a spike and wave on the EEG. A seizure
occurs when there is a massive depolarization of cells without intervening
periods of repolarization. This would
correspond to the tonic phase of the seizure. As inhibition increases during
the seizure, there is a cycle of PDS followed by repolarization. This corresponds to the clonic phase of the seizure
B. Examples of molecular targets of antiepileptic
drugs that reduce excitability. This may occur through blockage of calcium,
sodium, and potassium channels or
through reducing ion flow through NMDA and AMPA receptors. Levetiracetam binds
to synaptic vesicles, which may lead to reduced neurotrasnmiter release.
C. Examples of molecular targets of antiepileptic
drugs that enhance inhibition. Drugs may increase amount of GABA
postsynaptically by blocking GABA uptake
or increase intracellular GABA by reducing degradation of GABA. Enhancing
chloride flow through the GABA receptor is a common mechanism of inhibitory drugs, such as barbiturates and
benzodiazepines. Levetiracetam displaces zinc from the GABA receptor, which
results in increased chloride currents.
