cyclothiazide

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 477166277

| IUPAC_name = 3-(bicyclo[2.2.1]hept-5-en-2-yl)-6-chloro-1,1-dioxo-1,2,3,4-tetrahydro-1λ⁶,2,4-benzothiadiazine-7-sulfonamide

| image = Cyclothiazide.png

| tradename =

| pregnancy_category =

| legal_status = Rx-only

| routes_of_administration =

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| IUPHAR_ligand = 4167

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 2259-96-3

| ATC_prefix = C03

| ATC_suffix = AA09

| PubChem = 2910

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB00606

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

| ChemSpiderID = 4535011

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = P71U09G5BW

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D01256

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 61593

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

| smiles = O=S(=O)(c1c(Cl)cc2c(c1)S(=O)(=O)NC(N2)C4[C@@H]3\C=C/[C@@H](C3)C4)N

| 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 was subsequently also marketed in Europe and Japan.{{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}}{{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}} Related drugs include diazoxide, hydrochlorothiazide, and chlorothiazide.{{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}}

In 1993, it was discovered that cyclothiazide is a positive allosteric modulator of the AMPA and kainate receptors, capable of reducing or essentially eliminating rapid desensitization of the former receptor, and potentiating AMPA-mediated glutamate currents by as much as 18-fold at the highest concentration tested (100 μM).{{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 }}{{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 }}{{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}} Additionally, in 2003, cyclothiazide was also found to act as a GABA_A receptor negative allosteric modulator, potently inhibiting GABA_A-mediated currents.{{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 }} In animals it is a powerful convulsant, robustly enhancing epileptiform activity and inducing seizures, but without producing any apparent neuronal death.{{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 }}{{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 }}

Cyclothiazide has been found to act as a non-competitive antagonist of the mGluR1.{{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 }} It is selective for mGluR1 over other metabotropic glutamate receptors.