Atagabalin, also known as PD 0200390, is a gabamimetic agent under development for the treatment for insomnia. Atagabalin is related to gabapentin, which similarly binds to the α2δ calcium channels (1 and 2). It was discontinued following unsatisfactory t
ML218 hydrochloride is a selective and orally active T-type Ca2+ channels (Cav3.1, Cav3.2, Cav3.3) inhibitor (Cav3.2 and Cav3.3 with IC50s of 310 nM and 270 nM , respectively).
N-Arachidonoyl taurine is an arachidonoyl amino acid. It is oxygenated by 12(S)- and 15(S)-lipoxygenase and is converted to 12-HETE-taurine (12-HETE-T) in murine resident peritoneal macrophages. N-Arachidonoyl taurine is an activator of the transient receptor potential vanilloid (TRPV) channels TRPV1 and TRPV4 (EC50s = 28 and 21 μM, respectively). It increases calcium flux in HIT-T15 pancreatic β-cells and INS-1 rat islet cells when used at a concentration of 10 μM and increases insulin secretion from 832 13 INS-1 pancreatic β-cells. The levels of N-arachidonoyl taurine are changed in mouse brain following administration of δ9-tetrahydrocannabinol (δ9-THC).
5(6)-EET is a fully racemic version of the enantiomeric forms biosynthesized from arachidonic acid by cytochrome P450 enzymes. In solution, 5(6)-EET degrades into 5,6-DiHET and 5(6)-δ-lactone, which can be converted to 5(6)-DiHET and quantified by GC-MS. In neuroendocrine cells, such as the anterior pituitary and pancreatic islets, 5(6)-EET has been implicated in the mobilization of calcium and hormone secretion. 5(6)-EET is an inhibitor of T-type voltage-gated calcium channels (Cav3) that inhibits isoforms Cav3.1, Cav3.2 (IC50 = 0.54 μM), and Cav3.3 and decreases nifedipine-resistant phenylephrine-induced vasoconstriction in isolated mouse mesenteric arteries via Cav3.2 blockade when used at a concentration of 3 μM. In addition, it is a substrate of COX-1 and COX-2, as measured by oxygen consumption and product formation assays when used at a concentration of 50 μM. (±)5(6)-EET is provided as a mixture of the free acid and lactone.
Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide is an antiepileptic agent.1 It selectively inhibits the repeated firing of sodium channels (IC50 = 2 μg ml) in mouse embryo spinal cord neurons and inhibits spontaneous channel firing when used at concentrations greater than 10 μg ml.2 In rat cerebral cortex neurons, zonisamide (1-1,000 μM) inhibits T-type calcium channels with a maximum reduction of 60% of the calcium current.3 Zonisamide inhibits H. pylori recombinant carbonic anhydrase (CA) and the human CA isoforms I, II, and V with Ki values of 218, 56, 35, and 21 nM, respectively.4,5 In mice, it has anticonvulsant activity against maximal electroshock seizure (MES) and pentylenetetrazole-induced maximal, but not minimal, seizures (ED50s = 19.6, 9.3, and >500 mg kg, respectively). Zonisamide (40 mg kg, p.o.) prevents MPTP-induced decreases in the levels of dopamine , but not homovanillic acid or dihydroxyphenyl acetic acid , and increases MPTP-induced decreases in the dopamine turnover rate in mouse striatum in a model of Parkinson's disease.6 Formulations containing zonisamide have been used in the treatment of partial seizures in adults with epilepsy. |1. Masuda, Y., Ishizaki, M., and Shimizu, M. Zonisamide: Pharmacology and clinical efficacy in epilepsy. CNS Drug Rev. 4(4), 341-360 (1998).|2. Rock, D.M., Macdonald, R.L., and Taylor, C.P. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 3(2), 138-143 (1989).|3. Suzuki, S., Kawakami, K., Nishimura, S., et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 12(1), 21-27 (1992).|4. Nishimori, I., Vullo, D., Minakuchi, T., et al. Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylori. Bioorg. Med. Chem. Lett. 16(8), 2182-2188 (2006).|5. De Simone, G., Di Fiore, A., Menchise, V., et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 15(9), 2315-2320 (2005).|6. Yabe, H., Choudhury, M.E., Kubo, M., et al. Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP. J. Pharmacol. Sci. 110(1), 64-68 (2009).
TTA-P1 is a highly potent compound that effectively inhibits human T-type calcium channels, which are involved in various physiological processes such as neuronal burst firing, hormone secretion, and cell growth. With its unique state-independent properties, TTA-P1 holds promising potential for advancing research on absence epilepsy [1].