Cinazepam
(Synonyms: BD-798) 目录号 : GC47091An Analytical Reference Standard
Cas No.:172986-25-3
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
Cinazepam is an analytical reference standard categorized as a benzodiazepine.1 Cinazepam is a prodrug form of 3-hydroxy phenazepam that has anxiolytic and sedative properties. This product is intended for research and forensic applications.
1.Schukin, S.I., Zinkovsky, V.G., and Zhuk, O.V.Elimination kinetics of the novel prodrug cinazepam possessing psychotropic activity in micePharmacol. Rep.63(5)1093-1100(2011)
| Cas No. | 172986-25-3 | SDF | |
| 别名 | BD-798 | ||
| Canonical SMILES | BrC1=CC=C2C(C(C3=CC=CC=C3Cl)=NC(OC(CCC(O)=O)=O)C(N2)=O)=C1 | ||
| 分子式 | C19H14BrClN2O5 | 分子量 | 465.7 |
| 溶解度 | DMF: 15 mg/ml,DMF:PBS (pH 7.2) (1:9): 0.1 mg/ml,DMSO: 10 mg/ml,Ethanol: 0.2 mg/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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| 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。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1473 mL | 10.7365 mL | 21.4731 mL |
| 5 mM | 0.4295 mL | 2.1473 mL | 4.2946 mL |
| 10 mM | 0.2147 mL | 1.0737 mL | 2.1473 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
GABAA receptor agonist Cinazepam and its active metabolite 3-hydroxyphenazepam act differently at the presynaptic site
Eur Neuropsychopharmacol 2021 Apr;45:39-51.PMID:33820715DOI:10.1016/j.euroneuro.2021.03.013.
Cinazepam C19H14BrClN2O5, ("LevanaⓇ ІC") a partial GABAA receptor agonist, and its active metabolite 3-hydroxyphenazepam C15H10BrClN2O2 were comparatively assessed in vitro using nerve terminals isolated from rat cortex (synaptosomes). At the presynaptic site, Cinazepam (100 and 200 µM) facilitated synaptosomal transporter-mediated [3H]GABA uptake by enhancing both the initial rate and accumulation, and decreased the ambient level and transporter-mediated release of [3H]GABA. Whereas, 3-hydroxyphenazepam decreased the uptake and did not change the ambient synaptosomal level and transporter-mediated release of [3H]GABA. To exclude GABA transporter influence, NO-711, the transporter blocker, was applied and it was found that exocytotic release of [3H]GABA decreased, whereas tonic release of [3H]GABA was not changed in the presence of both Cinazepam or 3-hydroxyphenazepam after treatment of synaptosomes with NO-711. In fluorimetric studies using potential- and pH-sensitive dyes rhodamine 6G and acridine orange, respectively, it was found that Cinazepam hyperpolarized the synaptosomal plasma membrane, and increased synaptic vesicle acidification, whereas, 3-hydroxyphenazepam demonstrated opposite effects on these parameters. Therefore, action of Cinazepam and its active metabolite 3-hydroxyphenazepam on GABAergic neurotransmission was different. Therapeutic effects of Cinazepam can be associated with its ability to hyperpolarize the plasma membrane, to increase synaptic vesicle acidification and capacity of its active metabolite 3-hydroxyphenazepam to inhibit GABA transporter functioning.
Elimination kinetics of the novel prodrug Cinazepam possessing psychotropic activity in mice
Pharmacol Rep 2011;63(5):1093-100.PMID:22180351DOI:10.1016/s1734-1140(11)70628-4.
The kinetics of excretion of the novel tranquilizer Cinazepam (3-hydroxy-7-bromo-5-(ortho-chlorophenyl)-1,2-dihydro-3H-1,4-benzdiazepin-2-one hemisuccinate (I)) in mice after a single administration and different schemes of multiple administration were determined. Mass balance was studied daily in excretions of mice (feces and urine) for 5-10 days. We observed that monoexponential renal excretion of (14)C-cinazepam and its metabolites predominated with all dosage regimens. Cinazepam and its metabolites were almost fully (> 90%) eliminated in urine and feces over the period of study (5-10 days), which means that no significant accumulation of the drug in the body occurred. The kinetic parameters of drug excretion were not significantly different after a single injection compared with those following multiple doses of (14)C-cinazepam administration. This finding suggests the absence of induction (repression) of enzymatic systems after multiple administration and lack of influence on the kinetic scheme of Cinazepam elimination from mice. In our work, we also presented a modification of the Mansgeldorf's method for analysis of kinetic parameters during multiple administration of the tranquilizer. We demonstrated that our modified approach could be equally and efficiently applied for interpreting experimental data during a single dose administration and after chronic administration of xenobiotics. The use of this method made it possible to evaluate the relative efficiency of elimination processes and to find current values for excretion constants during sampling intervals.
Determination of Traditional and Designer Benzodiazepines in Urine through LC-MS/MS
Curr Pharm Des 2022;28(32):2622-2638.PMID:36045516DOI:10.2174/1381612828666220831103224.
Background: The detection of new designer benzodiazepines in biological fluids and tissues, together with the traditional ones, could represent an important analytical update for laboratories performing clinical and forensic toxicological analysis. Objective: A liquid chromatography tandem mass spectrometry method (LC-MS/MS) has been developed, fully validated, and applied to a cohort of real urine samples collected from patients under withdrawal treatment and from intoxication cases. Methods: 100 μL urines were added to a buffer solution containing deuterated internal standards; the samples were then extracted through a liquid/liquid procedure, dried under a nitrogen stream, and reconstituted in mobile phase. The chromatographic separation was performed in reverse phase through a C18 column with gradient elution. Mass spectrometry operated in positive polarization and multiple reaction monitoring mode. Results: 25 molecules were optimized for instrumental analysis: 9 designer benzodiazepines and 16 traditional compounds (parent drugs and main metabolites). Sensitivity, specificity, linearity, accuracy, imprecision, recovery, matrix effects, and carry-over have been evaluated for all molecules. Only Cinazepam did not satisfy all acceptance criteria for validation. 10 among the 50 analyzed samples tested positive for at least one of the monitored molecules. In particular, two different samples collected from the same case provided positive results for flubromazepam, a designer benzodiazepine. Conclusion: The method was proven to be useful in detecting not only traditional benzodiazepines but also new designer ones. The identification of a New Psychoactive Substance in real samples confirmed that analytical procedures should be updated to include as many substances as possible.
Racemization of oxazepam and chiral 1,4-benzodiazepines. DFT study of the reaction mechanism in aqueous solution
Org Biomol Chem 2019 Feb 6;17(6):1471-1479.PMID:30676597DOI:10.1039/c8ob02991a.
The tranquilizer and hypnotic drug oxazepam undergoes the racemization process in aqueous medium, which is relevant for its pharmacological profile. The experimental barrier value (ΔG‡298 ≈ 91 kJ mol-1) was determined earlier, but the exact mechanism of enantiomerization is not known. Four different mechanisms have been proposed in the literature: C3-H/H exchange reaction, keto-enol tautomerization, solvolytic identity reaction, and ring-chain tautomerization. However, none of the reported reactions has been confirmed as the main pathway for racemization. In this work, all these mechanisms were subjected to comprehensive analysis performed by high-level quantum-chemical models. Two density functionals (B3LYP and M062X) were employed for geometry optimization of all stationary points at the corresponding potential surfaces, and the double-hybrid model (B2PLYP) was used for improved energy calculations. Out of all the tested mechanisms, only the ring-chain tautomerism fits the two experimental targets: the measured energy barrier and the pH-rate profile of racemization. The latter reveals that no acid/base catalysis is required for racemization to occur. The ring-chain tautomerism is initiated by intramolecular proton transfer from the C3-hydroxyl group to the imine nitrogen, which triggers the benzodiazepine ring opening and the formation of the achiral aldehyde intermediate. The latter undergoes ring closure which results in the inverted configuration at the C3-chiral atom of oxazepam. Our computational results suggest that the same mechanism is operative in the fast racemization of different 1,4-benzodiazepines, which posses the hydroxyl group at the stereogenic C3-centre (e.g. lorazepam or temazepam). In other benzodiazepine members (e.g. Cinazepam or camazepam) the keto-enol tautomerization and/or the C3-H/H exchange mechanism may become relevant for their much slower racemization. This computational study is not only revealing in terms of mechanistic details, but also has predictive power for optical stability estimates in the family of benzodiazepines and similar heterocycles.
[The effect of 1,4-benzodiazepine derivatives on 35S-tert-butylbicyclophosphorothionate binding in the brain of inbred mice with differing emotional stress reactions]
Eksp Klin Farmakol 1997 Jul-Aug;60(4):3-6.PMID:9376753doi
The effect of alprazolam, Cinazepam, and hydazepam on the binding of 35S-tert-butylbicyclophosphorothionate with the brain membranes of inbred Balb/c and C57B1/6 mice with a different type of emotional-stress reaction was studied. The displacement curve of 35S-TBPS bound with alprazolam and Cinazepam was two-phase in character with different degree of inhibition in the nanomolar and micromolar areas. Hydazepam displaced the bound radioligand only in micromolar concentrations. Displacement of the bound radioligand in the brain membranes began with lower concentrations of the used benzodiazepins in Balb/c animals than in C57B1/6 animals. The emotional-stress effect led to shift of the displacement curves of the bound 35S-TBPS in the direction of higher acting concentrations of the benzodiazepins in the brain membranes of mice of both lines.