SV2A[1]
Seletracetam targets the synaptic vesicle glycoprotein 2A (SV2A), a membrane glycoprotein found on synaptic vesicles. SV2A plays a role in the regulation of neurotransmitter release and synaptic vesicle trafficking. Seletracetam binds to SV2A in a stereospecific and selective manner. By modulating SV2A function, seletracetam reduces excessive neuronal activity and restores the ability of a neuron to regulate its neurotransmitter release. This mechanism is thought to underlie its anticonvulsant effects.

Seletracetam interacts to the synaptic vesicle protein SV2A and reduces seizure activity in several epilepsy models[2]. Synaptic responses are reduced by seletracetam in a concentration-, frequency-, and time-dependent manner[2]. In vitro, seletracetam reduces intracellular Ca2+ accumulation and high-voltage-activated Ca2+ currents in rat cortical neurons[3].

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In vitro, seletracetam binds to SV2A in a stereospecific and selective manner. Synaptic responses are reduced by seletracetam in a concentration-, frequency-, and time-dependent manner. It is a small molecule SV2A modulator. In cell-based assays, seletracetam can modulate synaptic vesicle function and neurotransmitter release. Its binding affinity for SV2A is higher than that of levetiracetam, making it a more potent modulator.

In vivo, seletracetam decreases seizure activity in a number of epilepsy models. It is used for the research of epilepsy. By modulating SV2A function, seletracetam reduces excessive neuronal activity and restores the ability of a neuron to regulate its neurotransmitter release. The compound's anticonvulsant effects have been demonstrated in various preclinical models of epilepsy, including models of generalized and partial seizures.

Non-cellular in vitro assays for seletracetam involve receptor binding studies. A standard protocol uses membrane preparations from cells expressing recombinant human SV2A. The membranes are incubated with a radiolabeled ligand, such as [³H]levetiracetam or [³H]UCB30889, and varying concentrations of seletracetam. Non-specific binding is determined in the presence of an excess of unlabeled levetiracetam. After incubation, the reaction is terminated by rapid filtration, and the radioactivity bound to the membranes is measured. The Ki or IC50 values are calculated from the competition curves.

Cellular assays for seletracetam are performed using neuronal cell lines or primary neuronal cultures. Cells are treated with seletracetam at various concentrations. The modulation of SV2A function is assessed by measuring synaptic vesicle trafficking or neurotransmitter release. Alternatively, the compound's effects on neuronal excitability can be assessed using patch-clamp electrophysiology or by measuring calcium influx. The EC50 for modulation of SV2A function is determined.

In vivo animal studies for seletracetam are conducted in rodent models of epilepsy, such as the maximal electroshock seizure (MES) test, the pentylenetetrazole (PTZ) seizure test, or the kindling model. Animals are administered seletracetam orally or intraperitoneally at doses such as 1-30 mg/kg. The incidence and severity of seizures are measured. The compound's ability to reduce seizure activity is assessed. The duration of action is also evaluated.

Absorption, Distribution and Excretion
Celecene is rapidly absorbed after oral administration, reaching peak plasma concentration (Cmax) within 1 hour. Oral bioavailability is >90%. It is primarily excreted via the kidneys. The excretionate consists mainly of the parent drug (30%) and the acidic metabolite UCB-101596-1 (60%). The volume of distribution is approximately 0.6 L/kg, close to the total body water content. The apparent total clearance is approximately 0.8 mL/min/kg. Metabolism/Metabolites The acetamide group is hydrolyzed to form the carboxylic acid metabolite UCB-101596-1, which has no pharmacological activity. Biological Half-Life Approximately 8 hours in healthy young male subjects.

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Seletracetam has a molecular weight of 232.23 and a molecular formula of C10H14F2N2O2. It is a small molecule with drug-like properties. For in vivo studies, it can be formulated in standard vehicles for oral or intraperitoneal administration. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability have not been fully reported in the available literature. However, its efficacy in animal models suggests it has sufficient bioavailability to exert its effects.

Protein Binding

Indicated low plasma protein binding rate (<10%).

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Detailed toxicological data for seletracetam have not been extensively reported. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed when handling seletracetam, including the use of personal protective equipment. No specific toxicity data, such as LD50 values, are available in the provided literature.

[1]. Seletracetam, a small molecule SV2A modulator for the treatment of epilepsy. Curr Opin Investig Drugs. 2008 Jan;9(1):101-7.

[2]. Seletracetam (ucb 44212) inhibits high-voltage-activated Ca2+ currents and intracellular Ca2+ increase in rat cortical neurons in vitro. Epilepsia. 2009 Apr;50(4):702-10.

[3]. Seletracetam enhances short term depression in vitro. Epilepsy Res. 2015 Nov;117:17-22.

Seletracetam is an organic nitrogen and organic oxygen compound whose function is related to α-amino acids. Seletracetam is a pyrrolidone derivative with a structure similar to the next-generation antiepileptic drug levetiracetam. It binds to the same target as levetiracetam but with a higher affinity, showing potent seizure suppression in both acquired and genetic epilepsy models, and is well tolerated in the central nervous system. Low drug interactions are expected, and it will not inhibit or induce any major human metabolic enzymes. Seletracetam underwent Phase II clinical trials under the supervision of the U.S. Food and Drug Administration (FDA) to investigate its potential as a treatment for epilepsy and partial epilepsy, but its development was suspended in July 2007. As of 2010, production of Seletracetam was further halted due to the development of the novel antiepileptic drug buvaseristem. Drug Indications: Research for the treatment of epilepsy. Mechanism of Action: Seletracetam binds to SV2A in a stereospecific and selective manner. SV2A is a membrane glycoprotein found in neuronal synaptic vesicles that acts as a calcium regulator in neurotransmitter release and modulates synaptic networks. Celecene is thought to reduce overactive neuronal activity by modulating SV2A function and restoring the neuron's ability to regulate its neurotransmitter release. Seizures induce sustained membrane depolarization, leading to sustained voltage-dependent calcium current discharge sufficient to cause a significant increase in calcium ion concentration. Celecene inhibits this high-voltage activated calcium current by blocking N-type calcium channels in pyramidal neurons. The drug reduces calcium ion influx and intraneuronal calcium ion concentration, thereby blocking abnormal fluctuations in membrane potential that occur during epileptic discharges.

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Pharmacodynamics
Celeracetam is an antiepileptic drug that targets the presynaptic mechanism 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 an N-type calcium channel blocker, inhibiting aberrant neuronal firing by suppressing calcium channel function and associated calcium currents. Celecene significantly reduced epileptiform markers of hyperexcitability and hypersynchrony in in vitro epilepsy slice models and effectively suppressed seizures in in vivo epilepsy models simulating partial and generalized epilepsy.

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Seletracetam (UCB 44212) is a pyrrolidone-derived small molecule of the racetam family, structurally related to levetiracetam. It is a small molecule SV2A modulator for the research of epilepsy. Seletracetam binds to the synaptic vesicle protein SV2A in a stereospecific and selective manner. It decreases seizure activity in a number of epilepsy models. Seletracetam is not a clinically approved drug and has not entered clinical trials. Its primary application is in epilepsy research and the study of SV2A pharmacology.

C10H14F2N2O2

232.2308

232.102

C, 51.72; H, 6.08; F, 16.36; N, 12.06; O, 13.78

357336-74-4

Seletracetam lithium;Seletracetam lithium bromide;2024584-38-9

9942725

Off-white to light yellow solid powder

1.966

1

4

4

16

327

2

CC[C@@H](N1C[C@H](/C=C(\F)/F)CC1=O)C(=O)N

ANWPENAPCIFDSZ-RQJHMYQMSA-N

InChI=1S/C10H14F2N2O2/c1-2-7(10(13)16)14-5-6(3-8(11)12)4-9(14)15/h3,6-7H,2,4-5H2,1H3,(H2,13,16)/t6-,7+/m1/s1

(2S)-2-[(4S)-4-(2,2-difluoroethenyl)-2-oxopyrrolidin-1-yl]butanamide

UCB-44212; UCB44212; Seletracetam; 357336-74-4; UCB 44,212; UCB-44,212; RFR2CH3QZK; UCB 44212; Seletracetam

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~200 mg/mL (~861.22 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)