Clomethiazole
(Synonyms: 氯美噻唑) 目录号 : GC38758
Chlormethiazole 是一种有效的口服 GABAA 激动剂。 Chlormethiazole 还可以抑制人肝微粒体中的细胞色素 P450 亚型: CYP2A6 和 CYP2E1。Chlormethiazole 有抗惊厥作用，具有治疗惊厥性癫痫的潜力。
Cas No.:533-45-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Chlormethiazole is an potent and orally active GABAA agonist[1]. Chlormethiazole inhibits cytochrome P450 isoforms: CYP2A6 and CYP2E1 in human liver microsomes. Chlormethiazole is an anticonvulsant agent and has the potential for treating convulsive status epilepticus[2].
Clomethiazole (1 mM), in the absence of GABA, to α1/β1/γ2 or α1/β2/γ2 subunit-containing cells produced large whole-cell currents[1].Clomethiazole activate GABAA currents in α1/β1/γ2- and α1/β2/γ2-containing cells, with EC50 values of 0.3 and 1.5 mM, respectively[1].Clomethiazole (30 μM) at low concentration also potentiates the action of GABA in both cell types, equivalent to a 3-fold increase in potency and up to 1.8-fold increase in maximal current[1].Clomethiazole inhibits cytochrome P450 isoforms, CYP2A6 and CYP2E1 with IC50 values of 24 µM and 42 µM, respectively, in human liver microsomes, meanwhile all other isoforms exhibiting values > 300 µM[2].
[1]. Nelson RM, et al.Electrophysiological actions of gamma-aminobutyric acid and clomethiazole on recombinant GABA(A) receptors.Eur J Pharmacol. 2002 Oct 11;452(3):255-62. [2]. Stresser DM, et al. Selective Time- and NADPH-Dependent Inhibition of Human CYP2E1 by Clomethiazole.Drug Metab Dispos. 2016 Aug;44(8):1424-30
| Cas No. | 533-45-9 | SDF | |
| 别名 | 氯美噻唑 | ||
| Canonical SMILES | CC1=C(CCCl)SC=N1 | ||
| 分子式 | C6H8ClNS | 分子量 | 161.65 |
| 溶解度 | DMSO: 250 mg/mL (1546.55 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 6.1862 mL | 30.931 mL | 61.862 mL |
| 5 mM | 1.2372 mL | 6.1862 mL | 12.3724 mL |
| 10 mM | 0.6186 mL | 3.0931 mL | 6.1862 mL |
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动物数量 | 只 |
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2.
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Clomethiazole (Zendra) in acute ischemic stroke: basic pharmacology and biochemistry and clinical efficacy
Pharmacol Ther 1998 Nov;80(2):123-47.PMID:9839769DOI:10.1016/s0163-7258(98)00024-2.
This review discusses the efficacy of Clomethiazole (CMZ) in models of global and focal ischemia. The fact that neuroprotection is demonstrable by using histological, biochemical, and functional measures is emphasised. The importance of the neuroprotection observed when the drug is given after the ischemic insult and at doses that are safely tolerated by humans is discussed, with reference to requirements necessary for an experimental neuroprotective agent to be considered as a therapeutic drug for stroke. The biochemical pharmacology of CMZ is reviewed and also evaluated with reference to the possible mechanism(s) by which CMZ exerts its neuroprotective action. Finally, the clinical evidence that CMZ protects against the neurological consequences of a major stroke is outlined.
[Clomethiazole poisoning]
Z Rechtsmed 1984;93(2):89-94.PMID:6516604DOI:10.1007/BF00200767.
Clomethiazol can cause addiction, it can cause misbehavior in street traffic, and overdosage can lead to death. This paper presents 18 fatal cases in which clomethiazol played an essential role. This type of intoxication can be indicated by case history, easily identifiable tablets in the stomach contents, and a characterized odor. Since clomethiazol is easy to overlook during the general chemical analysis, a special gas chromatographical investigation should be made.
The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated stroke (CLASS-T): final results
Neurology 2001 Oct 9;57(7):1199-205.PMID:11591835DOI:10.1212/wnl.57.7.1199.
Objective: To assess the safety of tissue-type plasminogen activator (t-PA) plus Clomethiazole in patients with acute ischemic stroke and determine the feasibility of combination stroke therapy. Background: Clomethiazole is a neuroprotectant that appeared to improve outcome in patients with clinical deficits of a major stroke (total anterior circulation syndrome [TACS]) in a previous study, the Clomethiazole Acute Stroke Study (CLASS). Combining a neuroprotectant such as Clomethiazole with thrombolysis may augment the beneficial effects of the two agents. CLASS-t-PA (CLASS-T) was a pilot study to explore the safety of the combination and the feasibility of performing combination treatment in the setting of acute ischemic stroke. Methods: In a randomized, double-blind design (stratified for age, severity at admission, and time since onset of stroke), all patients received 0.9 mg/kg t-PA beginning within 3 hours of stroke onset and then either 68 mg/kg Clomethiazole (n = 97) IV over 24 hours or placebo (n = 93) beginning within 12 hours of stroke onset. Patients were followed for 90 days. The main measures of safety were mortality and serious adverse events, and the main measure of functional outcome was the Barthel Index. Results: The number of serious adverse event reports was 47 in the Clomethiazole group and 48 in the placebo group. Death during the 90 days after treatment occurred in 15 Clomethiazole and nine placebo patients (p = 0.26). Sedation was reported as an adverse event during therapy in 42% of Clomethiazole patients vs 13% of placebo patients. The proportion of patients with TACS was 53% in the Clomethiazole group and 41% in the placebo group. In the TACS subgroup, 52.9% of the Clomethiazole patients scored a Barthel Index greater than 60 vs 44.7% of placebo patients (odds ratio 1.39; 95% CI 0.60 to 3.23). Conclusion: In this pilot study, there were no safety concerns related to the combination of t-PA and Clomethiazole. The combination paradigm proved feasible, although many patients received Clomethiazole several hours after thrombolysis; future studies must require prompt administration of the neuroprotectant either before or during administration of the thrombolytic. Patients with major strokes (TACS) may have the potential to benefit from the combination of t-PA and Clomethiazole.
The metabolism of Clomethiazole in gerbils and the neuroprotective and sedative activity of the metabolites
Br J Pharmacol 2000 Jan;129(1):95-100.PMID:10694207DOI:10.1038/sj.bjp.0703042.
A single dose of Clomethiazole (600 micromol kg(-1) i.p.) has previously been shown to be neuroprotective in the gerbil model of global ischaemia. In gerbils, Clomethiazole (600 micromol kg(-1)) injection produced a rapid appearance (peak within 5 min) of drug in plasma and brain and similar clearance (plasma t(1/2): 40 min) from both tissues. The peak brain concentration (226+/-56 nmol g(-1)) was 40% higher than plasma. One major metabolite, 5-(1-hydroxyethyl-2-chloro)-4-methylthiazole (NLA-715) and two minor metabolites 5-(1-hydroxyethyl)-4-methylthiazole (NLA-272) and 5-acetyl-4-methylthiazole (NLA-511) were detected in plasma and brain. Evidence suggested that Clomethiazole is metabolized directly to both NLA-715 and NLA-272. Injection of NLA-715, NLA-272 or NLA-511 (each at 600 micromol kg(-1)) produced brain concentrations respectively 2.2, 38 and 92 times greater than seen after Clomethiazole (600 micromol kg(-1)). Clomethiazole (600 micromol kg(-1)) injected 60 min after a 5 min bilateral carotid artery occlusion in gerbils attenuated the ischaemia-induced degeneration of the hippocampus by approximately 70%. The metabolites were not neuroprotective at this dose. In mice, Clomethiazole (600 micromol kg(-1)) produced peak plasma and brain concentrations approximately 100% higher than in gerbils, drug concentrations in several brain regions were similar but 35% higher than plasma. Clomethiazole (ED(50): 180 micromol kg(-1)) and NLA-715 (ED(50): 240 micromol kg(-1)) inhibited spontaneous locomotor activity. The other metabolites were not sedative (ED(50) >600 micromol kg(-1)). These data suggest that the neuroprotective action of Clomethiazole results from an action of the parent compound and that NLA-715 contributes to the sedative activity of the drug. British Journal of Pharmacology (2000) 129, 95 - 100
Clomethiazole protects against hemineglect in a primate model of stroke
Brain Res Bull 2000 May 1;52(1):21-9.PMID:10779698DOI:10.1016/s0361-9230(99)00275-0.
Permanent occlusion of the M1 segment of the middle cerebral artery (pMCAO) in the marmoset, a New World species of monkey, produces unilateral functional deficits, including motor neglect with the contralesional arm and contralesional spatial hemineglect. In this study we examined whether Clomethiazole, a drug which modulates the gamma-aminobutyric acid(A) receptor, reduced the severity of the hemineglect and other deficits in this primate model of stroke. Nine monkeys received pMCAO; 1 h later four of the nine were administered Clomethiazole by intraperitoneal injection and subcutaneous implantation of osmotic mini-pumps, which released Clomethiazole for 48 h. The monkeys had been trained and tested on a number of behavioral tasks prior to surgery and were re-tested 3 and 10 weeks later. Three weeks after pMCAO, monkeys treated with Clomethiazole had a significantly reduced degree of spatial neglect compared to untreated controls. Clomethiazole was not effective against the severe contralesional motor impairment in the current study, although it ameliorated a somewhat less severe motor deficit in a previous study in which the more distal, M2 segment of the middle cerebral artery had been occluded. Postmortem analysis of the brains showed that Clomethiazole treatment had significantly reduced the area of damage in part of the parietal cortex. These data suggest that Clomethiazole may reduce the neglect that can be a debilitating consequence of right-sided stroke in man.