Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Cyclothiazide: Difference between pages

{{short description|Chemical compound}}

| verifiedrevid = 477166277

| IUPHAR_ligand = 4167

| DrugBank = DB00606

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 4535011

| ChEMBL = 61593

<!--Chemical data-->

| C=14 | H=16 | Cl=1 | N=3 | O=4 | S=2

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 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)/t7-,8+,9?,14?/m0/s1

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = BOCUKUHCLICSIY-QJWLJZLASA-N

'''Cyclothiazide''' ('''Anhydron''', '''Acquirel''', '''Doburil''', '''Fluidil''', '''Renazide''', '''Tensodiural''', '''Valmiran'''), sometimes abbreviated '''CTZ''', is a [[benzothiadiazide]] ([[thiazide]]) [[diuretic]] and [[antihypertensive]] that was originally introduced in the United States in 1963 by [[Eli Lilly and Company|Eli Lilly]] and was subsequently also marketed in [[Europe]] and [[Japan]].<ref name="isbn3-88763-075-0">{{cite book | author = Swiss Pharmaceutical Society | title = Index Nominum 2000: International Drug Directory (Book with CD-ROM) | publisher = Medpharm Scientific Publishers | location = Boca Raton | year = 2000 | pages = 1932 | isbn = 978-3-88763-075-1 | url = https://books.google.com/books?id=5GpcTQD_L2oC&q=Cyclothiazide&pg=PA287}}</ref><ref name="isbn0-8155-1144-2">{{cite book | vauthors = Sittig M | title = Pharmaceutical manufacturing encyclopedia | publisher = Noyes Publications | location = Park Ridge, N.J., U.S.A | year = 1988 | pages = 1756 | isbn = 978-0-8155-1144-1 | url = https://books.google.com/books?id=X2EyLsG4bcUC&q=Cyclothiazide&pg=PA418}}</ref> Related [[drug]]s include [[diazoxide]], [[hydrochlorothiazide]], and [[chlorothiazide]].<ref name="isbn0-8493-8307-2">{{cite book | vauthors = Skolnick P, Palfreyman MG, Reynolds IJ | title = Direct and allosteric control of glutamate receptors | publisher = CRC Press | location = Boca Raton | year = 1994 | pages = 174 | isbn = 978-0-8493-8307-6 | url = https://books.google.com/books?id=Fp9RLJTt7NkC&q=Cyclothiazide&pg=PA65}}</ref>

In 1993, it was discovered that cyclothiazide is a [[positive allosteric modulator]] of the [[AMPA receptor|AMPA]] and [[kainate receptor]]s, capable of reducing or essentially eliminating rapid [[desensitization (medicine)|desensitization]] of the former receptor, and potentiating AMPA-mediated [[glutamate]] currents by as much as 18-fold at the highest concentration tested (100 [[micromolar|μM]]).<ref name="isbn0-8493-8307-2"/><ref name="pmid8103555">{{cite journal | vauthors = Yamada KA, Tang CM | title = Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents | journal = The Journal of Neuroscience | volume = 13 | issue = 9 | pages = 3904–3915 | date = September 1993 | pmid = 8103555 | pmc = 6576449 | doi = 10.1523/JNEUROSCI.13-09-03904.1993 | doi-access = free }}</ref><ref name="pmid7915948">{{cite journal | vauthors = Bertolino M, Baraldi M, Parenti C, Braghiroli D, DiBella M, Vicini S, Costa E | title = Modulation of AMPA/kainate receptors by analogues of diazoxide and cyclothiazide in thin slices of rat hippocampus | journal = Receptors & Channels | volume = 1 | issue = 4 | pages = 267–278 | year = 1993 | pmid = 7915948 }}</ref><ref name="isbn3-540-22568-4">{{cite book | vauthors = Parsons CG, Danysz W, Zieglgänsberger W | chapter = Excitatory Amino Acid Neurotransmission | veditors = Ströhle A, Bilkei-Gorzo A, Holsboer F | title = Anxiety and anxiolytic drugs | publisher = Springer | location = Berlin | year = 2005 | pages = 566 | isbn = 978-3-540-22568-3 | chapter-url = https://books.google.com/books?id=RDP4_sBnsl4C&q=Cyclothiazide&pg=PA256}}</ref> Additionally, in 2003, cyclothiazide was also found to act as a [[GABAA receptor|GABA_A receptor]] [[negative allosteric modulator]], potently inhibiting GABA_A-mediated currents.<ref name="pmid14534329">{{cite journal | vauthors = Deng L, Chen G | title = Cyclothiazide potently inhibits gamma-aminobutyric acid type A receptors in addition to enhancing glutamate responses | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 22 | pages = 13025–13029 | date = October 2003 | pmid = 14534329 | pmc = 240738 | doi = 10.1073/pnas.2133370100 | doi-access = free | bibcode = 2003PNAS..10013025D }}</ref> In animals it is a powerful [[convulsant]], robustly enhancing [[epileptiform]] activity and inducing [[seizure]]s, but without producing any apparent [[neurotoxicity|neuronal death]].<ref name="pmid16423850">{{cite journal | vauthors = Qi J, Wang Y, Jiang M, Warren P, Chen G | title = Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons both in vitro and in vivo | journal = The Journal of Physiology | volume = 571 | issue = Pt 3 | pages = 605–618 | date = March 2006 | pmid = 16423850 | pmc = 1805799 | doi = 10.1113/jphysiol.2005.103812 }}</ref><ref name="pmid20678492">{{cite journal | vauthors = Kong S, Qian B, Liu J, Fan M, Chen G, Wang Y | title = Cyclothiazide induces seizure behavior in freely moving rats | journal = Brain Research | volume = 1355 | pages = 207–213 | date = October 2010 | pmid = 20678492 | pmc = 2947190 | doi = 10.1016/j.brainres.2010.07.088 }}</ref>

Cyclothiazide has been found to act as a [[non-competitive antagonist]] of the [[mGluR1]].<ref name="pmid17095021">{{cite journal | vauthors = Surin A, Pshenichkin S, Grajkowska E, Surina E, Wroblewski JT | title = Cyclothiazide selectively inhibits mGluR1 receptors interacting with a common allosteric site for non-competitive antagonists | journal = Neuropharmacology | volume = 52 | issue = 3 | pages = 744–754 | date = March 2007 | pmid = 17095021 | pmc = 1876747 | doi = 10.1016/j.neuropharm.2006.09.018 }}</ref> It is selective for mGluR1 over other [[metabotropic glutamate receptor]]s.<ref name="pmid17095021" />

==Synthesis==

[[File:Cyclothiazide synthesis.svg|thumb|center|700px|Cyclothiazide synthesis:<ref>{{Cite journal | doi = 10.1021/jo01066a046| title = Diuretics. V. 3,4-Dihydro-1,2,4-benzothiadiazine 1,1-Dioxides| journal = The Journal of Organic Chemistry| volume = 26| issue = 8| pages = 2814–2818| year = 1961| vauthors = Whitehead CW, Traverso JJ, Sullivan HR, Marshall FJ }}</ref><ref>{{cite patent | inventor = Müller E, Hasspacher K | country = US | number = 3275625 | gdate = 1966 | assign1 = [[Boehringer Ingelheim]] }}</ref>]]

== See also ==

* [[AMPA receptor positive allosteric modulator]]

== References ==

{{reflist}}

{{Diuretics}}

{{Navboxes

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[[Category:Diuretics]]

[[Category:Sulfonamides]]

[[Category:AMPA receptor positive allosteric modulators]]

[[Category:Kainate receptor agonists]]

[[Category:Benzothiadiazines]]

[[Category:Chloroarenes]]

[[Category:GABAA receptor negative allosteric modulators]]

[[Category:Carbonic anhydrase inhibitors]]

[[Category:Convulsants]]

[[Category:MGlu1 receptor antagonists]]

[[Category:Alkene derivatives]]