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| | CYCLOTHIAZIDE Basic information |
| Product Name: | CYCLOTHIAZIDE | | Synonyms: | 2,4-benzothiadiazine-3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-4-dihydro-2h-1;2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3,4-dihydro-6-chloro-3-(5-norbornen-2-yl)-,1,1-dioxide;2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-3,4-dihydro-, 1,1-dioxide;2h-1,2,4-benzothiadiazine-7-sulfonamide,3-bicyclo(2.2.1)hept-5-en-2-yl-6-chlor;35483;4-benzothiadiazine-7-sulfonamide,3,4-dihydro-6-chloro-3-(5-norbornen-2-2h-2;mdi193;o-3,4-dihydro-,1,1-dioxide | | CAS: | 2259-96-3 | | MF: | C14H16ClN3O4S2 | | MW: | 389.88 | | EINECS: | 218-859-7 | | Product Categories: | Glutamate;Glutamate receptor;Amines;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds | | Mol File: | 2259-96-3.mol |  |
| | CYCLOTHIAZIDE Chemical Properties |
| | CYCLOTHIAZIDE Usage And Synthesis |
| Description | Cyclothiazide (2259-96-3) is a positive allosteric modulator of AMPA receptors acting at a site distinct from that of 2,3-benzodiazepines.1,2 Clinically useful diuretic and antihypertensive agent.3 Induces robust epileptiform activity, inducing seizures but without neuronal death.4,5 Can be used to produce a new animal model for epilepsy.5 | | Originator | Anhydron,Lilly,US,1963 | | Uses | Diuretic; antihypertensive. A subunit-specific inhibitor of GABAC receptors. | | Uses | Cyclothiazide has been used as a α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) desensitization blocker to study the effects of γ2 on receptor desensitization. | | Definition | ChEBI: 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide substituted at positions 3, 5 and 6 by a 2-norbornen-5-yl group, chlorine, and a sulfonamide group, respectively. A thiazide diuretic, it has been used in the management of hypertension a
d oedema. | | Manufacturing Process | A mixture of 8.5 g (0.03 mol) of 6-chloro-4-amino-benzene-1,3-
disulfonamide, 4.0 g (0.033 mol) of 2,5-endomethylene-δ3-
tetrahydrobenzaldehyde and 25 cc of diethyleneglycol-dimethyl ether was
heated for 2 hours at 100°C. During this time the major portion of the initially
undissolved crystals went into solution; thereafter, the reaction mixture was
allowed to stand for 14 hours at room temperature, during which the
remaining undissolved crystals also went into solution. The reddish, clear
solution thus obtained was admixed with 50 cc of chloroform. The greyishwhite precipitate formed thereby was separated by vacuum filtration, washed
with a small amount of chloroform, dried and recrystallized from aqueous
methanol. 7.5 g of white crystalline needles having a melting point of 229° to
230°C were obtained. | | Brand name | Anhydron (Lilly). | | Therapeutic Function | Diuretic, Antihypertensive | | General Description | Cyclothiazide is a benzothiadiazine, which has a similar structure to diazoxide. | | Biological Activity | Positive allosteric modulator of AMPA receptors that potently inhibits AMPA receptor desensitization. Selective for the flip variant of each of the four receptor subunits. Also available as part of the AMPA Receptor Tocriset™ . | | Biochem/physiol Actions | Blocks the rapid desensitization of the AMPA glutamate receptors and markedly prolongs the decay time of the evoked excitatory post-synaptic current. | | storage | Room temperature | | References | 1) Donevan and Rogawski (1998), Allosteric regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors by thiocyanate and cyclothiazide at a common modulatory site distinct from that of 2,3-benzodiazepines; Neuroscience 87 615
2) Desai et al. (1995), Cyclothiazide acts at a site on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor complex that does not recognize competitive or noncompetitive AMPA receptor antagonists; J. Pharmacol. Exp. Ther. 272 38
3) Jeunemaitre et al. (1988), Long-term metabolic effects of spironolactone and thiazides combined with potassium-sparing agents for treatment of essential hypertension; Am. J. Cardiol. 62 1072
4) Qi et al. (2006), Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons both in vitro and in vivo; J. Physiol. 571 605
5) Kong et al. (2010), Cyclothiazide induces seizure behavior in freely moving rats; Brain Res. 1355 207 |
| | CYCLOTHIAZIDE Preparation Products And Raw materials |
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