Seletracetam
Seletracetam Uses, Dosage, Side Effects, Food Interaction and all others data.
Seletracetam is a pyrrolidone derivative and with a structural similarity to newer generation antiepileptic drug levetiracetam. It binds to the same target as levetiracetam but with higher affinity and has shown potent seizure suppression in models of acquired and genetic epilepsy with high CNS tolerability. It is predicted to have low drug-drug interactions and inhibition or induction of any major human metabolizing enzymes. Seletracetam was in Phase II clinical trials under the supervision of the U.S. Food and Drug Administration (FDA) investigated as treatment of epilepsy and partial epilepsy however its development had been put on hold in July 2007. As of 2010, its production was further halted due to the investigation of a newer antiepileptic agent, brivaracetam.
Seletracetam is an antiepileptic agent that targets the presynaptic mechanisms of epilepsy. It interferes with synaptic vesicle exocytosis and neurotransmitter release by binding to synaptic vesicle protein 2A (SV2A) which is involved in synaptic vesicle docking and fusion. It is also a N-type calcium channel blocker that inhibits the abnormal neuronal discharge by inhibiting the calcium channel function and associated calcium currents. Seletracetam markedly reduces epileptiform markers of both hyper-excitability and hyper-synchronization in an in vitro slice model of epilepsy and potently suppresses seizures in in vivo epilepsy models mimicking both partial and generalized epilepsy [A19305].
| Trade Name | Seletracetam |
| Generic | Seletracetam |
| Seletracetam Other Names | Seletracetam |
| Type | |
| Formula | C10H14F2N2O2 |
| Weight | Average: 232.2272 Monoisotopic: 232.102334112 |
| Protein binding | Demonstrates low plasma protein binding (<10%) |
| Groups | Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Investigated for use/treatment in epilepsy.
How Seletracetam works
Seletracetam binds to SV2A in a stereospecific and selective manner. SV2A is a membrane glycoprotein present in synaptic vesicles of neurons that plays a role as calcium regulators in neurotransmitter release and modulate synaptic networks. Seletracetam is thought to reduce excessive neuronal activity by modulating SV2A function and restoring the ability of a neuron to regulate its neurotransmitter release. Seizure generation induces a sustained membrane depolarization causing a prolonged firing of voltage-dependent calcium currents sufficient to induce a significant rise in calcium concentration. High voltage-activated calcium currents are inhibited by seletracetam by blocking N-type calcium channels in the pyramidal neurons. The drug reduces the degree of calcium influx and decreases the intraneuronal calcium concentration, blocking the abnormal fluctuations in membrane potential occurring during epileptic discharges.
Toxicity
High doses of 2000 mg/kg/day in the mouse and rat and ≥600 mg/kg/day in the dog were not well tolerated in animal studies. Seletracetam does not possess potential teratogenic, reproductive or embryonic toxicities. Most adverse effects are CNS-related effects, including somnolence, dizziness, feeling drunk, euphoria and nausea which all usually tend to be resolved within 24 hours.
Volume of Distribution
The volume of distribution is approximately 0.6 L/kg, which is close to that of total body water.
Elimination Route
Seletracetam is rapidly absorbed following oral administration, reaching the Cmax within 1 hour and displaying oral bioavailability of >90%.
Half Life
Approximately 8 hours in healthy young male subjects.
Clearance
The total apparent clearance is approximately 0.8mL/min/kg.
Elimination Route
Primarily eliminated through renal excretion. It is as mainly excreted as unchanged drug (30%) and an acidic metabolite ucb-101596-1 (60%).
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