Cyclothiazide

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Cyclothiazide
Cyclothiazide.png
Systematic (IUPAC) name
3-(bicyclo[2.2.1]hept-5-en-2-yl)-6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
Clinical data
Legal status Prescription only
Identifiers
CAS number 2259-96-3 YesY
ATC code C03AA09
PubChem CID 2910
DrugBank DB00606
ChemSpider 4535011 N
UNII P71U09G5BW YesY
KEGG D01256 YesY
ChEMBL CHEMBL61593 N
Chemical data
Formula C14H16ClN3O4S2 
Mol. mass 389.88 g/mol
 N (what is this?)  (verify)

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.[1][2] Related drugs include diazoxide, hydrochlorothiazide, and chlorothiazide.[3]

In 1993, it was discovered that cyclothiazide is a positive allosteric modulator of the AMPA receptor, capable of reducing or essentially eliminating rapid desensitization of the receptor, and potentiating glutamate currents by as much as 18-fold at the highest concentration tested (100 μM).[3][4][5][6] Additionally, in 2003, cyclothiazide was also found to act as a GABAA receptor negative allosteric modulator, potently inhibiting GABAA-mediated currents.[7] In animals it is a powerful convulsant, robustly enhancing epileptiform activity and inducing seizures, but without producing any apparent neuronal death.[8][9]

References[edit]

  1. ^ Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. p. 1932. ISBN 3-88763-075-0. 
  2. ^ Sittig, Marshall (1988). Pharmaceutical manufacturing encyclopedia. Park Ridge, N.J., U.S.A: Noyes Publications. p. 1756. ISBN 0-8155-1144-2. 
  3. ^ a b Skolnick, Phil; Palfreyman, Michael G.; Reynolds, Ian J. (1994). Direct and allosteric control of glutamate receptors. Boca Raton: CRC Press. p. 174. ISBN 0-8493-8307-2. 
  4. ^ Yamada KA, Tang CM (September 1993). "Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents". Journal of Neuroscience 13 (9): 3904–15. PMID 8103555. 
  5. ^ Bertolino M, Baraldi M, Parenti C, et al. (1993). "Modulation of AMPA/kainate receptors by analogues of diazoxide and cyclothiazide in thin slices of rat hippocampus". Receptors & Channels 1 (4): 267–78. PMID 7915948. 
  6. ^ Ströhle, Andreas; Bilkei-Gorzo, A.; Holsboer, Florian (2005). Anxiety and anxiolytic drugs. Berlin: Springer. p. 566. ISBN 3-540-22568-4. 
  7. ^ Deng L, Chen G (October 2003). "Cyclothiazide potently inhibits gamma-aminobutyric acid type A receptors in addition to enhancing glutamate responses". Proceedings of the National Academy of Sciences of the United States of America 100 (22): 13025–9. doi:10.1073/pnas.2133370100. PMC 240738. PMID 14534329. 
  8. ^ Qi J, Wang Y, Jiang M, Warren P, Chen G (March 2006). "Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons both in vitro and in vivo". The Journal of Physiology 571 (Pt 3): 605–18. doi:10.1113/jphysiol.2005.103812. PMC 1805799. PMID 16423850. 
  9. ^ Kong S, Qian B, Liu J, Fan M, Chen G, Wang Y (July 2010). "Cyclothiazide induces seizure behavior in freely moving rats". Brain Research 1355: 207–213. doi:10.1016/j.brainres.2010.07.088. PMC 2947190. PMID 20678492.