From the Guidelines
Keppra (levetiracetam) primarily acts as a synaptic vesicle protein 2A (SV2A) modulator, inhibiting excitatory neurotransmission by binding to SV2A and reducing the release of excitatory neurotransmitters such as glutamate. This mechanism of action is distinct from other antiepileptic medications, which often target voltage-gated sodium channels or GABA receptors 1. The binding of levetiracetam to SV2A is believed to stabilize neuronal activity and prevent the abnormal electrical discharges that lead to seizures.
Key Points About Keppra's Mechanism of Action
- Acts on synaptic vesicle protein 2A (SV2A) to modulate neurotransmitter release
- Inhibits the release of excitatory neurotransmitters like glutamate
- Has a unique mechanism of action compared to other antiepileptic drugs
- Helps in stabilizing neuronal activity and preventing abnormal electrical discharges As noted in a recent study published in Neuropsychopharmacology, SV2A modulators like levetiracetam are presumed to have inhibitory effects on excitatory neurotransmission, which is crucial for controlling seizures 1. This understanding of Keppra's mechanism of action supports its use as a valuable option for treating various types of epilepsy, with the added benefit of minimal drug interactions.
From the FDA Drug Label
The precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown. The antiepileptic activity of levetiracetam was assessed in a number of animal models of epileptic seizures Levetiracetam inhibits burst firing without affecting normal neuronal excitability, suggesting that levetiracetam may selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity Levetiracetam opposes the activity of negative modulators of GABA- and glycine-gated currents and partially inhibits N-type calcium currents in neuronal cells. A saturable and stereoselective neuronal binding site in rat brain tissue has been described for levetiracetam Experimental data indicate that this binding site is the synaptic vesicle protein SV2A, thought to be involved in the regulation of vesicle exocytosis These findings suggest that the interaction of levetiracetam with the SV2A protein may contribute to the antiepileptic mechanism of action of the drug.
The mechanism of action of levetiracetam is not fully understood. However, it is thought to involve the inhibition of burst firing and prevention of hypersynchronization of epileptiform burst firing and propagation of seizure activity. Levetiracetam may also oppose the activity of negative modulators of GABA- and glycine-gated currents and partially inhibit N-type calcium currents. Additionally, the interaction of levetiracetam with the SV2A protein may contribute to its antiepileptic mechanism of action 2.
- Key points:
- Inhibits burst firing
- Prevents hypersynchronization
- Opposes negative modulators of GABA- and glycine-gated currents
- Partially inhibits N-type calcium currents
- Interacts with SV2A protein
From the Research
Mechanism of Action of Keppra
The mechanism of action of Keppra (levetiracetam) involves several unique processes, including:
- Neuronal binding to synaptic vesicle protein 2A (SV2A) 3, 4, 5, 6, 7
- Inhibition of calcium release from intraneuronal stores 3, 4
- Opposition of the activity of negative modulators of GABA- and glycin-gated currents 3, 4
- Inhibition of excessive synchronized activity between neurons 3, 4
- Inhibition of N-type calcium channels 3, 4
Binding Characteristics
The binding characteristics of levetiracetam to SV2A have been studied in human brain and in CHO cells expressing the human recombinant protein 6. The results show that:
- The binding properties of levetiracetam are almost identical in human brain samples and in CHO cell membranes expressing the human SV2A protein 6
- The binding of levetiracetam to SV2A is saturable and reversible 6
- The binding kinetics are best fitted assuming a two-phase model 6
Clinical Implications
The unique mechanism of action of levetiracetam makes it an important addition to the treatment of epilepsy 5. The drug has been shown to be effective in controlling seizures in patients with partial-onset seizures, primary generalized tonic-clonic seizures, and myoclonic seizures of juvenile myoclonic epilepsy 3, 4, 5.