Levetiracetam (SIB-S1) is a relatively unique anticonvulsant that is typically used in combination with other antiepileptic medications for partial onset seizures. Levetiracetam has been linked to rare instances of serum aminotransferase and alkaline phosphatase elevations during treatment and to rare cases of clinically apparent drug induced liver disease.

Glycerol or glycerin is a colourless, odourless, viscous liquid that is sweet-tasting and mostly non-toxic. It is widely used in the food industry as a sweetener and humectant and in pharmaceutical formulations. Glycerol is an important component of trigl

Fluzinamide (AHR-8559) has anticonvulsant effects on ignited amygdala seizures.

Ameltolide is an anticonvulsant agent. It has been shown to be effective at inhibiting seizures in animal models.

Losigamone (AO-33) is an agonist of GABA receptor and can be used in studies about the treatment of partial seizures.

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

DL-Homocysteine thiolactone hydrochloride (DL-Homocysteinethiolactone hydrochloride) is a cysteine derivative that binds to and induces conformational changes in various plasma proteins, slowing coagulation and inducing oxidative stress. It decreases left ventricular systolic blood pressure and cardiac force and induces seizures in vivo.

GLUT1-IN-3 (Compd 4b), a compound under investigation for type 1 glucose transporter deficiency syndrome, effectively inhibits seizures [1].

Beclamide (Chlorakon) (N-benzyl-B-chloropropionamide) is a drug that possesses anticonvulsant activity. It is no longer used. It has been used as a sedative and as an anticonvulsant. It was studied in the 1950s for its anticonvulsant properties, as a treatment for generalized tonic-clonic seizures. It was not effective for absence seizures.

SGE516 is a neuroactive steroid and a positive allosteric modulator of both gamma- and delta-containing GABAA receptors. SGE516 reduces neuronal firing rates and epileptiform activity in vitro. SGE-516 protects against acute seizures and reduces neuronal

Prasterone is an endogenous steroid hormone. Prasterone acts as an agonist at ERβ, NMDA, and σ1 receptors, a partial agonist at ERα and AR, and antagonist at GABA-A receptors. It displays a variety of biologocial activities, including enhancing working me

Avermectin B1a aglycone is an aglycone form of the anthelmintic and insecticide avermectin B1a . It hyperpolarizes P. crassipes muscle fibers with a minimum active concentration (MAC) value of 0.1 μM. Avermectin B1a aglycone decreases survival of C. elegans (MAC = 0.1 μM). In vivo, avermectin B1a aglycone prevents seizures induced by pentylenetetrazole in mice (ED50 = 43.9 mg/kg) without inducing deficits in rotarod performance.

2-(Isopentylamino)naphthalene-1,4-dione is a vitamin K analog.1It inhibits spasms induced by pentylenetetrazole and tonic hindlimb extension induced by maximal electroshock (MES) in mice (ED50s = 349.2 and 108.1 mg/kg, respectively). It also protects mice against seizures in the 6 Hz psychomotor seizure test (ED50s = 152.7 and 263.7 mg/kg at stimulus intensities of 32 and 44 mA, respectively). 1.Li, X., Himes, R.A., Prosser, L.C., et al.Discovery of the first vitamin K analogue as a potential treatment of pharmacoresistant seizuresJ. Med. Chem.63(11)5865-5878(2020)

5α-Androst-16-en-3α-ol is a steroid pheromone that has been found in boar testes and human male axillary sweat and has diverse biological activities.1,2It enhances GABA-activated currents in primary mouse cerebellar granule cells (EC50= 0.4 μM).25α-Androst-16-en-3α-ol (0.1-1 μM) increases the amplitude of GABA-activated currents in HEK293 cells expressing human α1β2γ2and α2β2γ2subunit-containing GABAAreceptors.In vivo, 5α-androst-16-en-3α-ol (5-10 mg/kg) decreases immobility time in the forced swim test in mice. It increases time spent in the open arms of the elevated plus maze in mice, indicating anxiolytic-like activity, when administered at doses ranging from 30 to 50 mg/kg. 5α-Androst-16-en-3α-ol protects against seizures induced by pentylenetetrazole or electroshock in mice (ED50s = 48.9 and 21.9 mg/kg, respectively). 1.Brooksbank, B.W., Brown, R., and Gustafsson, J.A.The detection of 5α-androst-16-en-3α-ol in human male axillary sweatExperientia30(8)864-865(1974) 2.Kaminski, R.M., Marini, H., Ortinski, P.I., et al.The pheromone androstenol (5α-androst-16-en-3α-ol) is a neurosteroid positive modulator of GABAA receptorsJ. Pharmacol. Exp. Ther.317(2)694-703(2006)

L-803087 TFA is a highly potent and selective agonist of the somatostatin sst4 receptor, exhibiting a Ki value of 0.7 nM. It displays a remarkable selectivity, being over 280-fold more preferential for the sst4 receptor compared to other somatostatin receptors. Furthermore, L-803087 TFA promotes AMPA-mediated synaptic responses in hippocampal preparations and enhances kainate-induced seizures in mice.

Prilocaine (NSC-40027) is a local anesthetic of the amino amide type, which acts on the sodium channel on the neuronal membrane and limits the spread of seizures.

Trimethadione (3,5,5,-Trimethyloxazolidine-2,4-dione) is a dione-type anticonvulsant with antiepileptic activity.

Alpha,beta-Thujone, a constituent of various plant essential oils, has been linked to cancer development in male rats and can provoke seizures at maximal dosages [1].

α-Guanidinoglutaric Acid is found in cobalt-induced epileptogenic focus tissue in the cerebral cortex of cats. α-Guanidinoglutaric Acid-induced seizures are associated with abnormal serotonergic function and that they are initiated by a decrease in the 5-HT level.

α-Conotoxin ImI is a conotoxin that has been found inC. imperialisand has receptor antagonist and anticancer activities.1It is a peptide antagonist of homomeric α7 nicotinic acetylcholine receptors (nAChRs; IC50= 220 nM). α-Conotoxin ImI is selective for α7 nAChRs over α2β2, α3β2, α4β2, α2β4, α3β4, α4β4, and α1β1γδ subunit-containing nAChRs at 5 μM but does inhibit homomeric α9 nAChRs (IC50= 1,800 nM). Administration of paclitaxel in micelles containing α-conotoxin ImI decreases tumor growth in an MCF-7 mouse xenograft model.2Intracerebroventricular, but not intraperitoneal, administration of α-conotoxin ImI (20 nmol/animal) induces seizures in rats.3 1.Johnson, D.S., Martinez, J., Elgoyhen, A.B., et al.α-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: Preferential inhibition of homomeric α7 and α9 receptorsMol. Pharmacol.48(2)194-199(1995) 2.Mei, D., Lin, Z., Fu, J., et al.The use of α-conotoxin ImI to actualize the targeted delivery of paclitaxel micelles to α7 nAChR-overexpressing breast cancerBiomaterials4252-65(2015) 3.McIntosh, J.M., Yoshikami, D., Mahe, E., et al.A nicotinic acetylcholine receptor ligand of unique specificity, α-conotoxin ImIJ. Biol. Chem.269(24)16733-16739(1994)

Topiramate (RWJ 17021) is a unique antiseizure medication that is used in the treatment of partial and generalized seizures. Topiramate has been rarely associated with hepatic injury and largely when used in combination with other anticonvulsant medications.

10,11-Dihydro-10-hydroxycarbamazepine-d4 is a deuterated compound of 10,11-Dihydro-10-hydroxycarbamazepine. 10,11-Dihydro-10-hydroxycarbamazepine has a CAS number of 29331-92-8. Licarbazepine is the pharmacologically active metabolite of oxcarbazepine, a drug indicated for the treatment of partial seizures and bipolar disorders.

D-Leucine ((R)-Leucine) potently terminates seizures even after the onset of seizure activity. D-leucine reduces long-term potentiation but had no effect on basal synaptic transmission in vitro.

Pentadecanoyl ethanolamide, a derivative of the endogenous lipid amides (N-acylethanolamines), demonstrates anticonvulsant efficacy in electroshock-induced seizures in mice, exhibiting minimal toxicity [1].

10,11-Dihydro-10-hydroxy Carbamazepine-d4 is a deuterated compound of 10,11-Dihydro-10-hydroxy Carbamazepine. 10,11-Dihydro-10-hydroxy Carbamazepine has a CAS number of 29331-92-8. Licarbazepine is the pharmacologically active metabolite of oxcarbazepine, a drug indicated for the treatment of partial seizures and bipolar disorders.

N-(2-Chloro-6-methylphenyl)-N'-4-pyridinylurea is an anticonvulsant agent, treatment of generalized tonic-clonic and partial seizures.

Z944 is a T-type calcium channel blocker. Z944 delays the progression of seizures in the amygdala kindling model. Z944 disrupts prepulse inhibition in both epileptic and non-epileptic rats.

N-acetyl-2,3-dehydro-2-Deoxyneuraminic acid (DANA) is an inhibitor of human neuriminidases (sialidases) NEU1-4 (IC50s = 143, 43, 61, and 74 μM, respectively). In vivo, DANA (30 μL of a 5 mM solution) reduces latency to first seizure and increases seizure duration in a rat model of potassium-induced seizures.

L-803087 is a potent and selective agonist of the growth inhibitor sst4 receptor with a Ki value of 0.7 nM for sst4, which is more than 280-fold more selective than other growth inhibitory receptors.L-803087 induced AMPA-mediated synaptic responses in the hippocampus in vitro, and in vivo increased seizures in alginate-induced seizure-busting mice.

PF05020182 is novel potent and selective Kv7.2/4 potassium channel opener. PF-05020182 (2) significantly inhibits convulsions in the MES assay at doses tested, consistent with in vitro activity measure. The physiochemical properties, in vitro and in vivo activities of PF-05020182 support further development as an adjunctive treatment of refractory epilepsy. Facilitating activation, or delaying inactivation, of the native Kv7 channel reduces neuronal excitability, which may be beneficial in controlling spontaneous electrical activity during epileptic seizures.

Gabapentin hydrochloride (Neurontin HCl) is a GABA analogue, used to treat seizures and neuropathic pain.

AZD8797 (KAND567) is an orally available, selective and potent human CX3CR1-converting antagonist with inhibitory effects on CX3CR1 and CXCR2, and potentially protects against SARS-CoV-2-induced neuronal damage, preventing worsening of nociceptive sensitization and microglial activation in a migraine model of rats following seizures.

1. Decursin (Decursinol angelate) is able to attenuate kainic acid-induced seizures and could have potential as an antiepileptic drug. 2. Decursin exhibits hepatoprotective effects , potentially by inhibiting the TGF-β1 induced NOX activation and Smad signaling. 3. Decursin has anti-cancer activity , mediated suppression of the PKCα, MAPK and NF-κB pathways in MCF-7 cells. 4. Decursin exhibits cytotoxicity against various human cancer cells and to possess anti-amnesic activity in vivo through the inhibition of AChE activity.

Z-DEVD-FMK, a Caspase-3 Inhibitor, is an irreversible, cell-permeable inhibitor of caspase-3/CPP32 that impedes tumor cell apoptosis. In vivo studies show it offers neuroprotection in rat hippocampi post-seizures and considerably diminishes post-traumatic apoptosis, enhancing neurological recovery in rats before and after traumatic brain injury induction.

Sulfonadyn-47 is a dynamin inhibitor that effectively inhibits dynamin GTPase activity with an IC50 of 3.5 µM in cell-free assays. Additionally, it disrupts clathrin-mediated endocytosis in U2OS cells (IC50 = 27.3 µM) and impedes the depolarization-stimulated uptake of the synaptic vesicle endocytosis (SVE) marker FM4-64 in isolated rat brain synaptosomes (IC50 = 12.3 µM). Significantly, in vivo administration of sulfonadyn-47 at doses of 30 and 60 mg/kg demonstrates anticonvulsant properties in the 6 Hz corneal kindling mouse model of seizures.

Carbamazepine-10,11-epoxide-d10 (rings-d10) is a deuterated compound of Carbamazepine-10,11-epoxide. Carbamazepine-10,11-epoxide has a CAS number of 36507-30-9. Carbamazepine 10,11-epoxide is an active metabolite of the anticonvulsant carbamazepine[1][2].It is formed from carbamazepine by the cytochrome P450 (CYP) isoforms CYP3A4 and CYP2C8 in microsomes prepared from HepG2 cells expressing CYP3A4 or CYP2C8, respectively[1].Carbamazepine 10,11-epoxide has anticonvulsant activity against maximal electroshock-induced seizures in mice.2It has been found in wastewater effluent[3].

(S,S)-BD-AcAc 2 ((S,S)-Ketone Ester), an (S,S)-enantiomer of BD-AcAc 2, increases AcAc and acetone levels, inducing sustained ketosis and significantly delaying seizures associated with central nervous system oxygen toxicity (CNS-OT).

Dulozafone (F1933) has an anti- showed anticonvulsant activity in a brain amygdala ignition model and protected fully ignited rats from generalized seizures.

Carbamazepine 10,11-epoxide is an active metabolite of the anticonvulsant carbamazepine.1,2It is formed from carbamazepine by the cytochrome P450 (CYP) isoforms CYP3A4 and CYP2C8 in microsomes prepared from HepG2 cells expressing CYP3A4 or CYP2C8, respectively.1Carbamazepine 10,11-epoxide has anticonvulsant activity against maximal electroshock-induced seizures in mice.2It has been found in wastewater effluent.3 1.Kerr, B.M., Thummel, K.E., Wurden, C.J., et al.Human liver carbamazepine metabolism. Role of CYP3A4 and CYP2C8 in 10,11-epoxide formationBiochem. Pharmacol.47(11)1969-1979(1994) 2.Bourgeois, B.F., and Wad, N.Individual and combined antiepileptic and neurotoxic activity of carbamazepine and carbamazepine-10,11-epoxide in miceJ. Pharmacol. Exp. Ther.231(2)411-415(1984) 3.Miao, X.-S., Yang, J.-J., and Metcalfe, C.D.Carbamazepine and its metabolites in wastewater and in biosolids in a municipal wastewater treatment plantEnviron. Sci. Technol.39(19)7469-7475(2005)

(R)-4-Amino-3-hydroxybutyric acid, also known as (R)-GABOB, acts as a modulator of GABA receptors, specifically binding to both GABAA and GABAB receptors and blocking GABA reuptake in rat brain synaptosomes. Additionally, it serves as a GABAC receptor agonist, triggering currents in patch-clamp assays with Xenopus oocytes that express the human receptor. In vivo studies reveal its capability to suppress electrical discharges in the amygdala in cats undergoing N-amidinobenzamide-triggered seizures, indicating its potential therapeutic application in managing seizure disorders.

Eslicarbazepine Acetate (Zebinix) is an anticonvulsant medication approved for use in Europe, the United States and Canada as an adjunctive therapy for partial-onset seizures that are not adequately controlled with conventional therapy.

WWL123 is a potent and selective ABHD6 inhibitor (IC50=430 nM). WWL123 crosses the blood-brain-barrier and inhibits ABHD6 in brain parenchyma. ABHD6 blockade by WWL123 exerts an antiepileptic effect in Pentylenetetrazole (PTZ)-induced epileptiform seizures and spontaneous seizures in R6/2 mice.

Ethosuximide (Zarontin) is an anticonvulsant, blocks the low voltage-activated T-type calcium channel used in the treatment of absence seizures unaccompanied by other types of seizures.

Eslicarbazepine (Stedesa) can be used for adjunctive therapy for adults with partial-onset seizures.

CGP 37849 is a competitive orally active N-methyl-D-aspartate (NMDA) receptor antagonist ((Ki = 35 nM)) with potency.CGP 37849 is an anticonvulsant in rodents and also has antidepressant and anxiolytic properties.

Gabapentin-d6 Hydrochloride is a deuterated compound of Gabapentin Hydrochloride. Gabapentin Hydrochloride has a CAS number of 60142-95-2. Gabapentin HCl is a GABA analogue, used to treat seizures and neuropathic pain.

AK-IN-1, a competitive inhibitor for adenosine (Ado) but not for ATP, demonstrates significant inhibition of AK activity, achieving 86%, 87%, and 89% at concentrations of 2, 4, and 10 µM, respectively. This compound shows promise for research across various disease areas, such as ischemia, inflammation, and seizures.

CZL55 is a potent caspase-1 inhibitor with an IC50 value of 0.024 μM.CZL55 has low cytotoxicity and can be used in the study of febrile seizures (FS).

VU6007477 is a novel M1 PAM. VU6007477 resulted in good rat M1 PAM potency (EC50 = 230 nM, 93% ACh max), minimal M1 agonist activity (agonist EC50 > 10 μM), good CNS penetration (rat brain/plasma Kp = 0.28, Kp,uu = 0.32; mouse Kp = 0.16, Kp,uu = 0.18), and no cholinergic adverse events (AEs, e.g., seizures).

Pyrrole-2-carboxylic acid (Minaline) was first identified as a degradation product of sialic acids, then as a derivative of the oxidation of the D-hydroxyproline isomers by mammalian D-amino acid oxidase. The latter relationship results from the lability of the direct oxidation product, A'-pyrroline-4-hydroxy-2-carboxylic acid, which loses water spontaneously to form the pyrrole. A similar reaction is catalyzed by the more specific allohydroxy-D-proline oxidase of Pseudomonas. In whole animal observations, pyrrole-2-carboxylate (PCA) ' was identified in rat or human urine after administration of the D-isomers of hydroxyproline, a finding ascribable to the action of D-amino acid oxidase. Urinary excretion of N-(pyrrole-2-carboxyl) glycine has been reported in a 5-year-old affected with type II hyperprolinemia; The child has mild developmental delay, recurrent seizures of the grand mal type and EEG alterations.

Galanin (2-11) amide is a synthetic peptide fragment of the neuropeptide galanin and an agonist of the galanin-2 (GAL2) receptor (EC50= 9.32 nM in a fluorescence imaging plate reader assay).1It selectively binds to the GAL2receptor (IC50= 1.76 nM for the rat receptor) over the GAL1receptor (IC50= 879 nM for the human receptor) but does also bind to the GAL3receptor (Ki= 271 nM for the rat receptor).1,2Intracerebroventricular administration of galanin (2-11) amide (1 nmol/animal) decreases immobility in the forced swim test in rats.3It also reduces the hind paw mechanical pain threshold and increases the hind paw cold sensitivity threshold in rats.1

Peptide agonist for galanin receptors

Galanin is a neuropeptide with diverse biological activities. [1][2][3][4][5] It binds to rat galanin (GAL) receptor subtypes GAL1-3 (IC50s = 0.339, 1.35, and 3.31 nM, respectively) and human GAL1-3 (IC50s = 0.288, 1.62, and 12.3 nM, respectively). [1] Galanin binds to and inhibits contraction of guinea pig gastric smooth muscle cells induced by carbachol . [2] In vivo, Galanin (6 nmol, i.c.v.) increases feeding behavior in rats and increases latency to hindpaw withdrawal in response to heat and mechanical stimulation in a rat model of carrageenin-induced inflammation when administered at a dose of 2 nmol injected into the nucleus accumbens.[3][4] Galanin (5 μg, i.c.v.) also inhibits acetylcholine release induced by scopolamine in the ventral hippocampus of freely moving rats. [5]

N-terminal galanin fragment used to mediate central cardiovascular effects