t-currents

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.

Mibefradil is a calcium channel blocker with moderate selectivity for T-type Ca2+ channels (IC50s: 2.7 μM and 18.6 μM for T-type and L-type currents).

1-Octanol, a saturated fatty alcohol, functions as an inhibitor of T-type calcium channels (T-channels), showing an inhibitory concentration (IC50) of 4 μM for native T-currents[1]. Additionally, 1-Octanol is recognized for its potential as a biofuel, possessing diesel-like properties[2].

Azemiopsin, a potent inhibitor of the nicotinic acetylcholine receptor (nAChR), demonstrates half maximal inhibitory concentrations (IC50s) of 0.18 μM for T. californica nAChR and 22 μM for human α7 nAChR. Moreover, it effectively blocks acetylcholine-induced currents in Xenopus oocytes that heterologously express human muscle-type nAChR [1].

Oxodipine, a dihydropyridine-type calcium antagonist , inhibited KCl-induced aortic contraction in rabbits and reduced cardiac force in less potent rat ventricular test-paper contractions. In rat cultured neonatal ventricular myocytes, Oxodipine reduced L-type Ca currents (I) with an IC of 0.24 μM, and against T-type Ca currents (I) with an IC of 0.41 μM. Oxodipine causes constipation in mice and gingival hyperplasia in dogs.

Mibefradil dihydrochloride (Ro 40-5967 (dihydrochloride)) is an blocker of calcium channel with moderate selectivity for T-type Ca2+ channels (T-type and L-type currents with IC50s of 2.7 μM and 18.6 μM, respectively).

ShK toxin, isolated from the Caribbean sea anemone (Stichodactyla helianthus), is an inhibitor of the voltage-dependent potassium channel (Kv1.3 channel). It competes with dendrotoxin I and α-dendrotoxin in binding to rat brain synaptosomal membranes and promotes acetylcholine release. Additionally, ShK toxin reduces K+ currents in cultured rat dorsal root ganglion neurons and inhibits T lymphocyte proliferation [1] [2].

Zonisamide-d4 is a deuterated compound of Zonisamide. Zonisamide has a CAS number of 68291-97-4. Zonisamide, 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.

TTA-P2 (T-Type calcium channel inhibitor) is a potent inhibitor of the T-type calcium channel. TTA-P2 effectively penetrates the CNS and blocks natural T-type currents in deep cerebellar nucleus neurons, completely eliminating the window currents in wild-type and mutant Cav3.1 channels. research.

Extremely potent KV1.3 channel blocker (Kd = 23 pM for mKV1.3 currents). Selective for KV1.3 over other mammalian potassium channels (IC50 values are 23, 1800, 10500, 37000 and 39000 pM for mKV1.3, mKV1.1, hKV1.6, mKV1.4 and rKV1.2 respectively, and >1000

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).

Zonisamide sodium is a 1,2 benzisoxazole derivative. It is the first agent of this chemical class to be developed as an antiepileptic drug.