Cyclothiazide | CAS#2259-96-3

MedKoo Cat#: 317574 | Name: Cyclothiazide

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Cyclothiazide

CAS#2259-96-3

Theoretical Analysis

MedKoo Cat#: 317574

Name: Cyclothiazide

CAS#: 2259-96-3

Chemical Formula: C14H16ClN3O4S2

Exact Mass: 389.0271

Molecular Weight: 389.88

Elemental Analysis: C, 43.13; H, 4.14; Cl, 9.09; N, 10.78; O, 16.41; S, 16.45

Price and Availability

Size	Price	Availability
5mg	USD 250.00	Ready to ship
25mg	USD 750.00	2 Weeks
50mg	USD 1,350.00	2 weeks

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Synonym

Cyclothiazide; Anhydron; Renazide; Valmiran; Doburil; Fluidil; Anhydron; Acquirel; Renazide; Tensodiural

IUPAC/Chemical Name

3-(bicyclo[2.2.1]hept-5-en-2-yl)-6-chloro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide

InChi Key

BOCUKUHCLICSIY-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

C1C2CC(C1C=C2)C3NC4=CC(=C(C=C4S(=O)(=O)N3)S(=O)(=O)N)Cl

Appearance

Solid powder

Purity

>95% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# C9M05C02

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Cyclothiazide is a positive allosteric modulator of ionotropic α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors with critical roles in neurological development and function.

In vitro activity:

Manipulation of the excitability of XII MNs affects the amplitude but not the rate of ∫XII nerve bursts in the medullary slice. Inspiratory drive to these MNs is primarily AMPA-receptor dependent in vitro and is enhanced by acute CTZ exposure. To assess the long-term post-treatment effects of CTZ on inspiratory drive to XII MNs, currents were measured continuously from XII MNs before, during and up to 1 h post-treatment with 90 μm CTZ. CTZ was applied for only 10 min in order to reliably maintain stable whole-cell recordings for the duration of the experiment, while still getting reliable, though weaker, CIF, i.e. long-lasting facilitation of ∫XII nerve burst amplitude (Figs 3B and 4A). At 1 h post-treatment, endogenously generated drive to XII MNs was facilitated (Fig. 4A). Charge transfer was 153 ± 8.1% of pre-treatment (P < 0.001, n= 5, paired difference test) while ∫XII nerve burst amplitude increased to 146 ± 19% (P < 0.001, n= 5, paired difference test; Fig. 4B). Furthermore, the size of increase of ∫XII nerve burst amplitude correlated well with the increase in charge transfer (Fig. 4C). CTZ profoundly increased inspiratory ∫XII nerve burst amplitude in the respiratory rhythmic medullary slice preparation and modestly increased the burst rate. These results illustrate a latent residual capacity for potentiating AMPA-mediated inspiratory drive to XII MNs that might be applied to the treatment of upper airway motor deficits. Reference: J Physiol. 2012 Oct 1; 590(Pt 19): 4897–4915. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487044/

In vivo activity:

All the behavioral experiments were performed on freely moving rats at least 5 days after initial cannula implantation surgery. After surgery recovery, CTZ (0.25 μmol in 5 μL DMSO, once per day for consecutive 1-3 days) or DMSO alone (5 μL, once per day for 3 consecutive days) was slowly injected into the left ventricle via pre-implanted cannula in a 5 - 10 min time window. Consistent with the hypothesis, CTZ induced typical seizure behaviors in the majority of rats tested and in a dose-dependent manner (Table 1, Supplemental movie 1). Ranging from 10 to 30 minutes after CTZ injection, animals displayed abnormal behaviors such as rotation, salivating, eye blinking, and ear moving, followed by progressing to generalized seizures such as head nodding, unilateral forelimb clonus, rearing with bilateral forelimb clonus, rearing and falling, corresponding to Racine score II to V (Fig 1). All the animals in control group treated with DMSO didn't show such apparent seizure behaviors, except 2 out of 8 animals exhibiting facial automatisms (Racine I). In addition to inducing seizures in higher percentage of tested rats, high doses of CTZ also induced longer duration and more frequent seizure behaviors during our 3-hour testing period. Quantitative analysis revealed that CTZ dosedependently increased both the seizure number and seizure duration (Table 1 and Fig 2). Reference: Brain Res. 2010 Oct 8; 1355: 207–213. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947190/

	Solvent	mg/mL	mM
Solubility
	DMSO	24.5	62.83
	Ethanol	6.0	15.39

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 389.88 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Babiec WE, Faull KF, Feldman JL. Cyclothiazide-induced persistent increase in respiratory-related activity in vitro. J Physiol. 2012 Oct 1;590(19):4897-915. doi: 10.1113/jphysiol.2012.232421. Epub 2012 Jul 2. PMID: 22753547; PMCID: PMC3487044. 2. Qi J, Wang Y, Jiang M, Warren P, Chen G. Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons both in vitro and in vivo. J Physiol. 2006 Mar 15;571(Pt 3):605-18. doi: 10.1113/jphysiol.2005.103812. Epub 2006 Jan 19. PMID: 16423850; PMCID: PMC1805799. 3. Kong S, Qian B, Liu J, Fan M, Chen G, Wang Y. Cyclothiazide induces seizure behavior in freely moving rats. Brain Res. 2010 Oct 8;1355:207-13. doi: 10.1016/j.brainres.2010.07.088. Epub 2010 Jul 30. PMID: 20678492; PMCID: PMC2947190.

In vitro protocol:

In vivo protocol:

1. Kong S, Qian B, Liu J, Fan M, Chen G, Wang Y. Cyclothiazide induces seizure behavior in freely moving rats. Brain Res. 2010 Oct 8;1355:207-13. doi: 10.1016/j.brainres.2010.07.088. Epub 2010 Jul 30. PMID: 20678492; PMCID: PMC2947190. 2. Qi J, Wang Y, Jiang M, Warren P, Chen G. Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons both in vitro and in vivo. J Physiol. 2006 Mar 15;571(Pt 3):605-18. doi: 10.1113/jphysiol.2005.103812. Epub 2006 Jan 19. PMID: 16423850; PMCID: PMC1805799.

1: Farrow P, Khodosevich K, Sapir Y, Schulmann A, Aslam M, Stern-Bach Y, Monyer H, von Engelhardt J. Auxiliary subunits of the CKAMP family differentially modulate AMPA receptor properties. Elife. 2015 Dec 1;4. pii: e09693. doi: 10.7554/eLife.09693. [Epub ahead of print] PubMed PMID: 26623514. 2: Christiansen GB, Harbak B, Hede SE, Gouliaev AH, Olsen L, Frydenvang K, Egebjerg J, Kastrup JS, Holm MM. A novel dualistic profile of an allosteric AMPA receptor modulator identified through studies on recombinant receptors, mouse hippocampal synapses and crystal structures. Neuroscience. 2015 Dec 3;310:709-22. doi: 10.1016/j.neuroscience.2015.09.073. Epub 2015 Oct 9. PubMed PMID: 26450748. 3: Galvao J, Elvas F, Martins T, Cordeiro MF, Ambrósio AF, Santiago AR. Adenosine A3 receptor activation is neuroprotective against retinal neurodegeneration. Exp Eye Res. 2015 Nov;140:65-74. doi: 10.1016/j.exer.2015.08.009. Epub 2015 Aug 18. PubMed PMID: 26297614. 4: Samengo IA, Currò D, Martire M. Nicotinic receptors modulate the function of presynaptic AMPA receptors on glutamatergic nerve terminals in the trigeminal caudal nucleus. Neurochem Int. 2015 Nov;90:166-72. doi: 10.1016/j.neuint.2015.08.008. Epub 2015 Aug 12. PubMed PMID: 26277383. 5: Eisenman LN, Emnett CM, Mohan J, Zorumski CF, Mennerick S. Quantification of bursting and synchrony in cultured hippocampal neurons. J Neurophysiol. 2015 Aug;114(2):1059-71. doi: 10.1152/jn.00079.2015. Epub 2015 Jun 3. PubMed PMID: 26041823. 6: Rigby M, Cull-Candy SG, Farrant M. Transmembrane AMPAR regulatory protein γ-2 is required for the modulation of GABA release by presynaptic AMPARs. J Neurosci. 2015 Mar 11;35(10):4203-14. doi: 10.1523/JNEUROSCI.4075-14.2015. PubMed PMID: 25762667; PubMed Central PMCID: PMC4355196. 7: Park YH, Mueller BH 2nd, McGrady NR, Ma HY, Yorio T. AMPA receptor desensitization is the determinant of AMPA receptor mediated excitotoxicity in purified retinal ganglion cells. Exp Eye Res. 2015 Mar;132:136-50. doi: 10.1016/j.exer.2015.01.026. Epub 2015 Jan 30. PubMed PMID: 25643624. 8: McNair LF, Kohlmeier KA. Prenatal nicotine is associated with reduced AMPA and NMDA receptor-mediated rises in calcium within the laterodorsal tegmentum: a pontine nucleus involved in addiction processes. J Dev Orig Health Dis. 2015 Jun;6(3):225-41. doi: 10.1017/S2040174414000439. Epub 2014 Nov 3. PubMed PMID: 25362989. 9: Wan L, Liu X, Wu Z, Ren W, Kong S, Dargham RA, Cheng L, Wang Y. Activation of extrasynaptic GABA(A) receptors inhibits cyclothiazide-induced epileptiform activity in hippocampal CA1 neurons. Neurosci Bull. 2014 Oct;30(5):866-76. doi: 10.1007/s12264-014-1466-8. Epub 2014 Sep 28. PubMed PMID: 25260800. 10: Bukhari SA, Shamshari WA, Ur-Rahman M, Zia-Ul-Haq M, Jaafar HZ. Computer aided screening of secreted frizzled-related protein 4 (SFRP4): a potential control for diabetes mellitus. Molecules. 2014 Jul 11;19(7):10129-36. doi: 10.3390/molecules190710129. PubMed PMID: 25019556.

Description:

Chemical Structure

Theoretical Analysis

Price and Availability

Preparing Stock Solutions

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