Epilepsy

Y-27632 dihydrochloride is an orally active and ATP-competitive ROCK (Rho-kinase) inhibitor (ROCK-I K_i=220 nM; ROCK-II K_i=300 nM). Y-27632 dihydrochloride shows antiepileptic effects.

D-Galactose is a natural aldohexose and C-4 epimer of glucose.

Valproic acid (VPA) is an orally active HDAC inhibitor, with IC₅₀ in the range of 0.5 and 2 mM. Valproic acid inhibits HDAC1 (IC₅₀, 400 μM), and induces proteasomal degradation of HDAC2. Valproic acid activates Notch1 signaling and inhibits proliferation in small cell lung cancer (SCLC) cells. Valproic acid is used in the epilepsy, bipolar disorder, metabolic disease, HIV infection and prevention of migraine headaches.

Belnacasan (VX-765) is an orally bioactive proagent of VRT-043198, which is a potent and selective inhibitor of IL-converting enzyme (ICE)/caspase-1 with K_is of 0.8 nM and less than 0.6 nM for caspase-1 and caspase-4, respectively. Belnacasan (VX-765) inhibits the release of LPS-induced IL-1β and IL-18 by human PBMCs with an IC₅₀ of ~0.7 μM.

Kainic acid is a potent excitotoxic agent. Kainic acid hydrate also is an agonist for a subtype of ionotropic glutamate receptor. Kainic acid induces seizures.

Stiripentol (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to NCLB mediatated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with K_i of 1.59±0.07 and 0.516±0.065 μM and IC₅₀ of 1.58 and 3.29 μM, respectively.

L-Aspartic acid is a NMDA receptor agonist and acidic amino acid. L-Aspartic acid has no independent analgesic activity. L-Aspartic acid can antagonize the analgesic effects of D-Aspartic acid and Morphine. L-Aspartic acid regulates polymorph transformation, crystal growth/aggregation and nucleation processes of calcium carbonate, and can serve as a biomineralization template. L-Aspartic acid promotes burst firing of central neurons. L-Aspartic acid can be used in studies related to cerebral ischemia and epilepsy.

Tranexamic acid (cyclocapron), a cyclic analog of lysine, is an orally active antifibrinolytic agent. Tranexamic acid attenuates the effects of severe trauma, inhibits urokinase plasminogen activator and ameliorates dry wrinkles. Tranexamic acid can used for the research of hemostasis. Tranexamic acid is a PROTAC linker. Tranexamic acid is used to synthesize PROTACs (e.g. LZ-07 (HY-172590)).

Bicuculline ((+)-Bicuculline) is A competing neurotransmitter GABA_A receptor antagonist (IC₅₀=2 μM). Bicuculline also blocks Ca²⁺ activating potassium (SK) channels and subsequently blocks slow post-hyperpolarization (slow AHP). Bicuculline has anticonvulsant activity. Bicuculline can be used to induce seizures in mice.

Fasudil (HA-1077; AT877) Hydrochloride is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an K_i of 0.33 μM for ROCK1, IC₅₀s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM for ROCK2 and PKA, PKC, PKG, respectively. Fasudil Hydrochloride is also a potent Ca²⁺ channel antagonist and vasodilator.

Gabapentin is a potent, orally active P/Q type Ca²⁺ channel blocker. Gabapentin inhibits neuronal Ca²⁺ influx and reduction of neurotransmitter release. Gabapentin is a GABA analog that can be used to relieve neuropathic pain.

Carbamazepine is an orally active pressure-sensitive sodium ion channel blocker with an IC₅₀ of 131 μM. Carbamazepine blocks voltage gated Na⁺, Ca²⁺, and K⁺ channels, and is also a HDAC inhibitor (IC₅₀: 2 μM). Carbamazepine is an anticonvulsant and can be used for research of epilepsy and neuropathic pain.

MOG (35-55) mouse, rat (Myelin Oligodendrocyte Glycoprotein Peptide (35-55), mouse, rat) is a minor component of CNS myelin. MOG (35-55) mouse, rat has encephalitogenic activity and induces T cell proliferative. MOG (35-55) mouse, rat induces Th1 cytokine response as well as relatively high levels of IgG antibodies. MOG (35-55) mouse, rat produces a relapsing-remitting neurological disease with extensive plaque-like demyelination. MOG (35-55) mouse, rat (MOG (35-55)) can be used for experimental autoimmune encephalomyelitis (EAE) modeling.

L-Methionine-DL-sulfoximine (MSX; MSO), a highly specific and irreversible inhibitor of Glutamine synthetase (GS), is also a potent convulsant which metabolically and morphologically primarily affects astroglia. L-Methionine-DL-sulfoximine has been employed to inhibit the Gln-dependent ammonia-stimulated neuronal toxicity in vitro, potentiating Gln deficit-dependent depression. L-Methionine-DL-sulfoximine tremendously increases the rate of release of fixed nitrogen in cyanobacteria. L-Methionine-DL-sulfoximine is a promising candidate for research in biofertilizers and convulsive seizures (CS).

NBQX (FG9202) is a highly selective and competitive AMPA receptor antagonist. NBQX has neuroprotective and anticonvulsant activity.

Withaferin A is a steroidal lactone isolated from Withania somnifera, inhibits NF-kB activation and targets vimentin, with potent antiinflammatory and anticancer activities. Withaferin A is an inhibitor of endothelial protein C receptor (EPCR) shedding.

Atorvastatin hemicalcium salt (CI-981) is an orally active 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, with blood-brain barrier permeability. Atorvastatin hemicalcium salt has the ability to effectively decrease blood lipids. Atorvastatin hemicalcium salt inhibits human SV-SMC proliferation and invasion with IC₅₀s of 0.39 μM and 2.39 μM, respectively.

Quinidine (15% dihydroquinidine) is an orally active antiarrhythmic agent. Quinidine (15% dihydroquinidine) reduces the expression level of P-gp, inhibits P-gp-mediated efflux, increases the intracellular accumulation of P-gp substrates, induces PARP cleavage and Caspase-3 activation, and elevates the proportion of Apoptotic cells at the sub-G1 phase. Quinidine (15% dihydroquinidine) exerts sustained block and open-channel block effects on I_K(f). Quinidine (15% dihydroquinidine) alters the urinary metabolic ratio of Amphetamine, modulates the Pentylenetetrazol-induced seizure threshold, and regulates the anticonvulsant effect of Dextromethorphan. Quinidine (15% dihydroquinidine) can be used in studies related to uterine sarcoma and seizures.

Vigabatrin (γ-Vinyl-GABA), an inhibitory neurotransmitter GABA vinyl-derivative, is an orally active and irreversible GABA transaminase inhibitor. Vigabatrin is an antiepileptic agent, which acts by increasing GABA levels in the brain by inhibiting the catabolism of GABA by GABA transaminase.

Azetukalner (XEN1101) is a selective and orally active Kv7.2/Kv7.3 potassium channel opener with an EC₅₀ of 27 nM. Azetukalner is approximately 4-fold more selective for Kv7.2/7.3 over Kv7.3/7.5 (EC₅₀ of 94 nM) and Kv7.4 (EC₅₀ of 113 nM) channels. Azetukalner exhibits a selectivity >100-fold for Kv7 channels over other ion channels and receptors. Azetukalner can be used for the study of focal epilepsy.