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| Other Sizes |
| Targets |
The primary targets of 2,2,2-Trichloroethanol are the nonclassical two-pore domain potassium (K2P) channels TREK-1 (KCNK2) and TRAAK (KCNK4), for which it acts as an agonist. It also interacts with the 5-hydroxytryptamine3A (5-HT3A) receptor, where arginine 246 of the pretransmembrane domain 1 region alters its action. These targets mediate the compound's sedative-hypnotic effects and its vasodilatory actions on cerebral blood vessels.
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| ln Vitro |
2,2,2-Trichloroethanol causes the middle cerebral artery to dilate and opens non-classical potassium channels in the cerebral vascular smooth muscle [1].
In vitro, 2,2,2-Trichloroethanol activates nonclassical potassium channels in cerebrovascular smooth muscle cells, leading to membrane hyperpolarization and relaxation of vascular smooth muscle. This results in dilation of the middle cerebral artery, which is consistent with its effects on cerebral blood flow. The compound also modulates 5-HT3A receptor function in vitro. These activities make it a useful tool for studying potassium channel physiology and the pharmacology of sedative-hypnotic agents in isolated tissue preparations. |
| ln Vivo |
In vivo, 2,2,2-Trichloroethanol produces sedative-hypnotic effects as the active metabolite of chloral hydrate. It causes dilation of the middle cerebral artery by opening nonclassical potassium channels in cerebrovascular smooth muscle. The compound's in vivo effects include central nervous system depression, hypnosis, and sedation. Animal studies have demonstrated its efficacy in inducing sleep and reducing anxiety-like behaviors. The compound is also used to study cerebrovascular regulation and the role of K2P channels in vascular tone.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for 2,2,2-Trichloroethanol involve incubating the compound with cell membranes or purified receptor preparations to assess its binding affinity and agonist activity at TREK-1 and TRAAK channels. Radioligand binding assays using labeled channel ligands can determine binding affinity (Ki values). Electrophysiological recordings using patch-clamp techniques are the gold standard for measuring channel activation, with compound concentrations typically ranging from 0.1-100 mM. The effects on 5-HT3A receptors can be assessed using similar electrophysiological approaches. Appropriate controls including known channel blockers are included.
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| Cell Assay |
In vitro cell-based assays for 2,2,2-Trichloroethanol utilize cultured cerebrovascular smooth muscle cells or heterologous expression systems (e.g., HEK293 cells) expressing TREK-1 or TRAAK channels. Cells are treated with compound concentrations ranging from 0.01-50 mM for various durations. Channel activity is measured using patch-clamp electrophysiology or fluorescent membrane potential dyes. Cell viability is assessed using standard assays such as MTT. The compound's effects on intracellular calcium levels and cell signaling pathways can also be measured. Experiments include vehicle controls and positive controls (e.g., known K2P channel agonists).
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| Animal Protocol |
In vivo animal studies with 2,2,2-Trichloroethanol are typically conducted in rodents (mice or rats) to assess sedative-hypnotic effects and cerebrovascular function. The compound is administered via intraperitoneal or intravenous injection at doses ranging from 50-400 mg/kg. Sedation is assessed using the loss of righting reflex test or open field activity monitoring. Cerebral blood flow is measured using laser Doppler flowmetry or MRI-based techniques. The duration of action and dose-response relationships are determined. Each treatment group consists of 6-10 animals, with vehicle-treated groups serving as controls.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
Trichloroethanol is a known human metabolite of trichloroethane. Pharmacokinetic properties of 2,2,2-Trichloroethanol include its formation as the active metabolite of chloral hydrate through hepatic alcohol dehydrogenase-mediated reduction. It has good oral bioavailability and distributes widely in body tissues, including the brain, where it exerts its sedative-hypnotic effects. The plasma half-life in humans is approximately 8-12 hours. Metabolism occurs primarily through oxidation to trichloroacetic acid or glucuronidation, with elimination via renal excretion. The compound's pharmacokinetics are dose-dependent, with saturation of elimination pathways at higher doses. |
| Toxicity/Toxicokinetics |
Toxicological data for 2,2,2-Trichloroethanol indicate that it can cause central nervous system depression, respiratory depression, and cardiac arrhythmias at high doses. Chronic exposure may lead to hepatotoxicity and nephrotoxicity. The compound is classified as a potential carcinogen based on studies of its prodrug chloral hydrate. Acute overdose can result in coma, hypotension, and respiratory failure. The therapeutic index is relatively narrow, and the compound should be handled with appropriate safety precautions in research settings.
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| References | |
| Additional Infomation |
2,2,2-Trichloroethanol is a chloroethanol. It plays a metabolic role in mice. It has also been reported that 2,2,2-trichloroethanol exists in cattle (Bos taurus) and Euglena gracilis, and relevant data are available.
2,2,2-Trichloroethanol is the active metabolite of the sedative-hypnotic drug chloral hydrate, which has been used clinically for insomnia and sedation. It is not approved as a standalone therapeutic agent but is used in research to study K2P potassium channel function, sedative-hypnotic mechanisms, and cerebrovascular regulation. The compound is also utilized in studies of 5-HT3A receptor pharmacology. Its vasodilatory effects on cerebral arteries make it relevant to cerebrovascular research. For research use only; not for human therapeutic applications. |
| Molecular Formula |
C₂H₃CL₃O
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|---|---|
| Molecular Weight |
149.40
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| Exact Mass |
147.924
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| CAS # |
115-20-8
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| PubChem CID |
8259
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| Appearance |
Colorless to light yellow liquid
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
152.1±35.0 °C at 760 mmHg
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| Melting Point |
17.8 °C(lit.)
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| Flash Point |
45.8±25.9 °C
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| Vapour Pressure |
1.3±0.6 mmHg at 25°C
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| Index of Refraction |
1.499
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| LogP |
1.38
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
6
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| Complexity |
38.5
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC(C([H])([H])O[H])(Cl)Cl
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| InChi Key |
KPWDGTGXUYRARH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C2H3Cl3O/c3-2(4,5)1-6/h6H,1H2
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| Chemical Name |
2,2,2-trichloroethanol
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| Synonyms |
2,2,2Trichloroethanol; 2,2,2 Trichloroethanol
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~669.34 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (16.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (16.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (16.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.6934 mL | 33.4672 mL | 66.9344 mL | |
| 5 mM | 1.3387 mL | 6.6934 mL | 13.3869 mL | |
| 10 mM | 0.6693 mL | 3.3467 mL | 6.6934 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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