Ethopropazine (hydrochloride)
(Synonyms: 盐酸乙丙嗪,Isothazine hydrochloride; Lysivane hydrochloride; Parsidol hydrochloride) 目录号 : GC47314
A BChE inhibitor
Cas No.:1094-08-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Ethopropazine is a butyrylcholinesterase (BChE) inhibitor (IC50 = 15.14 µM in human erythrocyte lysates).1 It is selective for BChE over acetylcholinesterase (AChE) at 500 µM. Ethopropazine also binds to rat forebrain and hindbrain membrane preparations (Kis = 3.1 and 7.2 nM, respectively), which are endogenously enriched in M1 and M2 muscarinic acetylcholine receptors, respectively.2 Ethopropazine (0.232 mg/kg) decreases the intensity and increases the latency of haloperidol-induced catalepsy, a model of extrapyramidal syndrome, in rats when used in combination with the adenosine A2A receptor antagonist ZM 241395 .3 It reduces thermal hyperalgesia in a rat model of neuropathic pain induced by sciatic nerve ligation when administered at doses of 20 and 30 mg/kg.4 Formulations containing ethopropazine were previously used in the treatment of Parkinson's disease.
1.Ucar, G., Gokhan, N., Yesilada, A., et al.1-N-Substituted thiocarbamoyl-3-phenyl-5-thienyl-2-pyrazolines: a novel cholinesterase and selective monoamine oxidase B inhibitors for the treatment of Parkinson's and Alzheimer's diseasesNeurosci. Lett.382(3)327-331(2005) 2.Burke, R.E.The relative selectivity of anticholinergic drugs for the M1 and M2 muscarinic receptor subtypesMov. Disord.1(2)135-144(1986) 3.GonzÁlez-Lugo, O.E., Ceballos-Huerta, F., JimÉenez-Capdeville, M.E., et al.Synergism of theophylline and anticholinergics to inhibit haloperidol-induced catalepsy: A potential treatment for extrapyramidal syndromesProg. Neuropsychopharmacol. Biol. Psychiatry34(8)1465-1471(2010) 4.Jevtovic-Todorovic, V., Meyenburg, A.P., Olney, J.W., et al.Anti-parkinsonian agents procyclidine and ethopropazine alleviate thermal hyperalgesia in neuropathic ratsNeuropharmacology44(6)739-748(2003)
| Cas No. | 1094-08-2 | SDF | |
| 别名 | 盐酸乙丙嗪,Isothazine hydrochloride; Lysivane hydrochloride; Parsidol hydrochloride | ||
| Canonical SMILES | CC(N(CC)CC)CN1C2=C(C=CC=C2)SC3=CC=CC=C31.Cl | ||
| 分子式 | C19H24N2S.HCl | 分子量 | 348.9 |
| 溶解度 | DMF: 10mg/mL,DMF:PBS (pH 7.2) (1:5): 0.16mg/mL,DMSO: 5mg/mL,Ethanol: 5mg/mL | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8662 mL | 14.3308 mL | 28.6615 mL |
| 5 mM | 0.5732 mL | 2.8662 mL | 5.7323 mL |
| 10 mM | 0.2866 mL | 1.4331 mL | 2.8662 mL |
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Mechanism of stereoselective interaction between butyrylcholinesterase and Ethopropazine enantiomers
Biochimie 2011 Oct;93(10):1797-807.PMID:21740955DOI:10.1016/j.biochi.2011.06.023.
Stereoselectivity of reversible inhibition of butyrylcholinesterase (BChE; EC 3.1.1.8) by optically pure Ethopropazine [10-(2-diethylaminopropyl)phenothiazine hydrochloride] enantiomers and racemate was studied with acetylthiocholine (0.002-250 mM) as substrate. Molecular modelling resulted in the reaction between BChE and Ethopropazine starting with the binding of Ethopropazine to the enzyme peripheral anionic site. In the next step Ethopropazine 'slides down' the enzyme gorge, resulting in interaction of the three rings of Ethopropazine through π-π interactions with W82 in BChE. Inhibition mechanism was interpreted according to three kinetic models: A, B and C. The models differ in the type and number of enzyme-substrate, enzyme-inhibitor and enzyme-substrate-inhibitor complexes, i.e., presence of the Michaelis complex and/or acetylated BChE. Although, all three models reproduced well the BChE activity in absence of Ethopropazine, model A was poor in describing inhibition with Ethopropazine, while models B and C were better, especially for substrate concentrations above 0.2 mM. However model C was singled out because it approaches fulfilment of the one step-one event criteria, and confirms the inhibition mechanism derived from molecular modelling. Model C resulted in dissociation constants for the complex between BChE and Ethopropazine: 61, 140 and 88 nM for R-enantiomer, S-enantiomer and racemate, respectively. The respective dissociation constants for the complexes between acetylated BChE and Ethopropazine were 268, 730 and 365 nM. Butyrylcholinesterase had higher affinity for R-ethopropazine.
Kinetic model of Ethopropazine interaction with horse serum butyrylcholinesterase and its docking into the active site
Arch Biochem Biophys 2002 Feb 1;398(1):23-31.PMID:11811945DOI:10.1006/abbi.2001.2697.
The action of a potent tricyclic cholinesterase inhibitor Ethopropazine on the hydrolysis of acetylthiocholine and butyrylthiocholine by purified horse serum butyrylcholinesterase (EC 3.1.1.8) was investigated at 25 and 37 degrees C. The enzyme activities were measured on a stopped-flow apparatus and the analysis of experimental data was done by applying a six-parameter model for substrate hydrolysis. The model, which was introduced to explain the kinetics of Drosophila melanogaster acetylcholinesterase [Stojan et al. (1998) FEBS Lett. 440, 85-88], is defined with two dissociation constants and four rate constants and can describe both cooperative phenomena, apparent activation at low substrate concentrations and substrate inhibition by excess of substrate. For the analysis of the data in the presence of Ethopropazine at two temperatures, we have enlarged the reaction scheme to allow primarily its competition with the substrate at the peripheral site, but the competition at the acylation site was not excluded. The proposed reaction scheme revealed, upon analysis, competitive effects of Ethopropazine at both sites; at 25 degrees C, three enzyme-inhibitor dissociation constants could be evaluated; at 37 degrees C, only two constants could be evaluated. Although the model considers both cooperative phenomena, it appears that decreased enzyme sensitivity at higher temperature, predominantly for the ligands at the peripheral binding site, makes the determination of some expected enzyme substrate and/or inhibitor complexes technically impossible. The same reason might also account for one of the paradoxes in cholinesterases: activities at 25 degrees C at low substrate concentrations are higher than at 37 degrees C. Positioning of Ethopropazine in the active-site gorge by molecular dynamics simulations shows that A328, W82, D70, and Y332 amino acid residues stabilize binding of the inhibitor.
Extractive spectrophotometric determination of tungsten(VI) in alloy steels using Ethopropazine hydrochloride
Anal Sci 2002 Aug;18(8):913-5.PMID:12200839DOI:10.2116/analsci.18.913.
Ethopropazine hydrochloride (EPH) has been proposed as a sensitive reagent for the spectrophotometric determination of tungsten(VI). The method is based on the formation of a chloroform-soluble yellow-colored ternary complex by the interaction of EPH and thiocyanate with tungsten(V). The complex exhibits the absorption maximum at 404 nm with Sandell's sensitivity value of 20.03 ng cm-2. The complex obeyed Beer's law in the concentration range of 1-15 micrograms ml-1 with an optimum concentration range of 2.3-12.9 micrograms ml-1. The effects of foreign ions in the determination of tungsten(VI) were investigated. The method has also been successfully applied to the analysis of alloy steels.
Pharmacokinetics of Ethopropazine in the rat after oral and intravenous administration
Biopharm Drug Dispos 1999 Apr;20(3):159-63.PMID:10211869DOI:10.1002/(sici)1099-081x(199904)20:3<159::aid-bdd164>3.0.co;2-d.
The pharmacokinetics of the anticholinergic drug Ethopropazine (ET) have been studied in the rat after intravenous (i.v.) and oral administration. After i.v. doses of 5 and 10 mg/kg ET HCl, mean +/- S.D. plasma AUC were 9836 +/- 2129 (n = 4 rats) and 13096 +/- 4186 ng h/mL (n = 5 rats), respectively. The t1/2 after 5 and 10 mg/kg i.v. doses were 17.9 +/- 3.3 and 20.9 +/- 6.0 h, respectively. The Cl and V(dss) after 5 mg/kg i.v. doses were 0.48 +/- 0.10 L/h/kg and 7.1 +/- 2.3 L/kg, respectively. Statistically significant differences were present between the 5 and 10 mg/kg dose levels in Cl and V(dss). Oral administration of 50 mg/kg ET HCl (n = 5 rats) yielded mean AUC of 2685 +/- 336 ng h/mL. Mean plasma C(max), t(max) and t1/2 after oral doses were 236 +/- 99 ng/mL, 2.2 +/- 1.4 h and 26.1 +/- 5.4 h, respectively. Less than 1% of the dose was recovered unchanged in urine and bile. Ethopropazine is extensively distributed in the rat, and has relatively slow Cl in relation to hepatic blood flow in the rat. The drug appears to be extensively metabolized in the rat, and nonlinearity is present between the 5 and the 10 mg/kg i.v. doses. The drug displayed poor bioavailability (< 5%) after oral administration.
Separation, conformation in solution and absolute configuration of Ethopropazine enantiomers
Enantiomer 2002 Mar-Jun;7(2-3):149-56.PMID:12108633DOI:10.1080/10242430212188.
Enantiomers of Ethopropazine x HCl (10-(2-diethylaminopropyl)phenothiazine hydrochloride) were prepared by fractional crystallization of diastereomeric dibenzoyltartaric acid salts, and their optical purity (enantiomeric excess, ee) determined by HPLC on Chiralcel OJ column. With a solvent mixture n-hexane/t-butanol/triethylamine (100:3:0.5) as eluent a very good enantioseparation (alpha = 1.68) for racemic Ethopropazine was obtained. Enantiomeric purity for (-)-enantiomer was 99.1% and for (+)-enantiomer 97.9%. Combined data from NMR and CD spectra of both enantiomers, along with previously reported X-ray structure analyses of racemic Ethopropazine, revealed skewed conformation of tricyclic system in solution, and (S)-configuration on the stereogenic center for (-)-enantiomer, and (R)-configuration for (+)-enantiomer.