Cyclothiazide

• CAT Number: R011543
• CAS Number: 2259-96-3
• Molecular Formula: C14H16ClN3O4S2
• Molecular Weight: 389.869
• Purity: ≥95%
• Target: AMPAR
• Solubility: Soluble in DMSO > 10 mM
• Storage: Store at RT
• IUPAC Name: 3-(5-bicyclo[2.2.1]hept-2-enyl)-6-chloro-1,1-dioxo-3,4-dihydro-2H-1$l^{6}
• InChI: InChI=1S/C14H16ClN3O4S2/c15-10-5-11-13(6-12(10)23(16,19)20)24(21,22)18-14(17-11)9-4-7-1-2-8(9)3-7/h1-2,5-9,14,17-18H,3-4H2,(H2,16,19,20)
• InChIKey: BOCUKUHCLICSIY-UHFFFAOYSA-N
• SMILES: C1C2CC(C1C=C2)C3NC4=CC(=C(C=C4S(=O)(=O)N3)S(=O)(=O)N)Cl

Cyclothiazide (Anhydron, Acquirel, Doburil, Fluidil, Renazide, Tensodiural, Valmiran) is a benzothiadiazide (thiazide) diuretic and antihypertensive that was originally introduced in the United States in 1963 by Eli Lilly and was subsequently also marketed in Europe and Japan. This agent is capable of inhibiting rapid desensitization of the ionotropic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors, thereby potentiating glutamate responses which may induce seizures activity. Cyclothiazide was also found to inhibit gamma-aminobutyric acid (GABA)-A receptors.

Reference

1:Activation of extrasynaptic GABA(A) receptors inhibits cyclothiazide-induced epileptiform activity in hippocampal CA1 neurons. Wan L, Liu X, Wu Z, Ren W, Kong S, Dargham RA, Cheng L, Wang Y.Neurosci Bull. 2014 Oct;30(5):866-76. doi: 10.1007/s12264-014-1466-8. Epub 2014 Sep 28. PMID: 25260800 2:Downregulated GABA and BDNF-TrkB pathway in chronic cyclothiazide seizure model. Kong S, Cheng Z, Liu J, Wang Y.Neural Plast. 2014;2014:310146. doi: 10.1155/2014/310146. Epub 2014 Mar 13. PMID: 24757570 Free PMC Article3:Cyclothiazide-induced persistent increase in respiratory-related activity in vitro. Babiec WE, Faull KF, Feldman JL.J Physiol. 2012 Oct 1;590(19):4897-915. doi: 10.1113/jphysiol.2012.232421. Epub 2012 Jul 2. PMID: 22753547 Free PMC Article4:Epileptiform response of CA1 neurones to convulsant stimulation by cyclothiazide, kainic acid and pentylenetetrazol in anaesthetized rats. Qian B, Sun Y, Wu Z, Wan L, Chen L, Kong S, Zhang B, Zhang F, Wang ZY, Wang Y.Seizure. 2011 May;20(4):312-9. doi: 10.1016/j.seizure.2010.12.016. Epub 2011 Jan 26. PMID: 21269843 Free Article5:Cyclothiazide induces seizure behavior in freely moving rats. Kong S, Qian B, Liu J, Fan M, Chen G, Wang Y.Brain Res. 2010 Oct 8;1355:207-13. doi: 10.1016/j.brainres.2010.07.088. Epub 2010 Jul 30. PMID: 20678492 Free PMC Article6:Distinct structural features of cyclothiazide are responsible for effects on peak current amplitude and desensitization kinetics at iGluR2. Hald H, Ahring PK, Timmermann DB, Liljefors T, Gajhede M, Kastrup JS.J Mol Biol. 2009 Sep 4;391(5):906-17. doi: 10.1016/j.jmb.2009.07.002. Epub 2009 Jul 8. PMID: 19591837 7:BDNF-TrkB signaling pathway mediates the induction of epileptiform activity induced by a convulsant drug cyclothiazide. Wang Y, Qi JS, Kong S, Sun Y, Fan J, Jiang M, Chen G.Neuropharmacology. 2009 Jul;57(1):49-59. doi: 10.1016/j.neuropharm.2009.04.007. Epub 2009 Apr 22. PMID: 19393251 Free PMC Article8:Cyclothiazide binding to the GABAA receptor. Szárics E, Simon A, Visy J, Simon-Trompler E, Banka Z, Héja L, Hársing LG, Blaskó G, Kardos J.Neurosci Lett. 2008 Jul 4;439(1):66-9. doi: 10.1016/j.neulet.2008.04.092. Epub 2008 May 2. PMID: 18502046 9:Cyclothiazide: a subunit-specific inhibitor of GABAC receptors. Xie A, Song X, Ripps H, Qian H.J Physiol. 2008 Jun 1;586(11):2743-52. doi: 10.1113/jphysiol.2008.153346. Epub 2008 Apr 17. PMID: 18420703 Free PMC Article10:Alpha2 subunit specificity of cyclothiazide inhibition on glycine receptors. Zhang XB, Sun GC, Liu LY, Yu F, Xu TL.Mol Pharmacol. 2008 Apr;73(4):1195-202. Epub 2007 Dec 27. Erratum in: Mol Pharmacol. 2008 Jun;73(6):1866. PMID: 18162605 Free Article