(S)-Venlafaxine
(Synonyms: 文拉法辛S-异构体) 目录号 : GC60424
(S)-Venlafaxine是Venlafaxine的S构型化合物。Venlafaxine是口服有效的5-羟色胺(5-HT)/去甲肾上腺素(NE)重摄取的双重抑制剂。Venlafaxine具有抗抑郁作用。
Cas No.:93413-44-6
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
(S)-Venlafaxine is the (S)-configuration of Venlafaxine. Venlafaxine is an orally active, potent serotonin (5-HT)/norepinephrine (NE) reuptake dual inhibitor. Venlafaxine is an antidepressant agent[1].
[1]. Bymaster FP, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80.
| Cas No. | 93413-44-6 | SDF | |
| 别名 | 文拉法辛S-异构体 | ||
| Canonical SMILES | OC1([C@@H](C2=CC=C(OC)C=C2)CN(C)C)CCCCC1 | ||
| 分子式 | C17H27NO2 | 分子量 | 277.4 |
| 溶解度 | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.6049 mL | 18.0245 mL | 36.049 mL |
| 5 mM | 0.721 mL | 3.6049 mL | 7.2098 mL |
| 10 mM | 0.3605 mL | 1.8025 mL | 3.6049 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。
Enantioselective Ecotoxicity of Venlafaxine in Aquatic Organisms: Daphnia and Zebrafish
Environ Toxicol Chem 2022 Aug;41(8):1851-1864.PMID:35452529DOI:10.1002/etc.5338.
Venlafaxine is a chiral antidepressant detected in aquatic compartments. It was recently included in the 3rd Watch List from the European Union. The present study aimed to investigate venlafaxine toxicity effects, targeting possible enantioselective effects, using two aquatic organisms, daphnia (Daphnia magna) and zebrafish (Danio rerio). Specimens were exposed to both racemate, (R,S)-Venlafaxine (VEN), and to pure enantiomers. Acute assays with daphnia showed that up to 50 000 μg/L of the (R,S)-VEN induced no toxicity. Organisms were also exposed to sublethal concentrations (25-400 μg/L) of (R,S)-, (R)- and (S)-VEN, for 21 days. No significant effects on mortality, age at first reproduction, and size of the first clutch were observed. However, a decrease in fecundity was observed for both enantiomers at the highest concentration. Regarding zebrafish, the effects of venlafaxine on mortality, embryo development, behavior, biochemistry, and melanin pigmentation were investigated after 96 h of exposure to the range of 0.3-3000 μg/L. (R)-VEN significantly increased the percentage of malformations in comparison with (S)-VEN. Behavior was also enantiomer dependent, with a decrease in the total distance moved and an increase in avoidance behavior observed in organisms exposed to (R)-VEN. Despite the biochemical variations, no changes in redox homeostasis were observed. (R)-VEN also led to an increase in zebrafish pigmentation. The different susceptibility to venlafaxine and enantioselective effects were observed in zebrafish. Our results suggest that at environmental levels (R,S)-VEN and pure enantiomers are not expected to induce harmful effects in both organisms, but (R)-VEN increased malformations in zebrafish larvae, even at reported environmental levels. These results highlight the importance of including enantioselective studies for an accurate risk assessment of chiral pollutants. Environ Toxicol Chem 2022;41:1851-1864. © 2022 SETAC.
Establishing bioequivalence of racemic venlafaxine formulations using stereoselective assay method: Is it necessary?
Chirality 2011 Nov;23(10):948-54.PMID:21953854DOI:10.1002/chir.21021.
A bioequivalence study for venlafaxine generic formulation was conducted as an open label, balanced, randomized, two-way crossover, single-dose study. In this study, a comparison of various pharmacokinetic parameters of venlafaxine hydrochloride 150 mg modified release capsules of Ranbaxy and EFEXOR®-XR 150 mg capsules of Wyeth, in healthy, adult, male, human subjects under fasting condition was performed to conclude bioequivalence. Venlafaxine and its major active metabolite O-desmethylvenlafaxine (ODV) are racemates. The "(S)-(+)" and "(R)-(-)" enantiomers of venlafaxine and ODV are established as being active. Hence, subject samples were analyzed using nonstereoselective and stereoselective assay methods. Both (S)-(+) and (R)-(-) enantiomers of venlafaxine and ODV showed similar absorption and disposition. The 90% confidence intervals for venlafaxine, (R)-(-)-Venlafaxine as well as (S)-(+)-Venlafaxine were within acceptance range concluding bioequivalence. The results obtained by stereoselective assay were comparable to the nonstereoselective analysis, as sum of concentrations of (S)-(+)- and (R)-(-)-enantiomers of venlafaxine and ODV. The mean (S)-(+)/(R)-(-) ratios of the enantiomers of venlafaxine and ODV at various time points were consistent in the study subjects. Therefore, the estimation of venlafaxine and ODV using nonstereoselective assay method is effective in distinguishing formulation differences (if any) in bioequivalence studies in a cost-effective manner.
The disposition of venlafaxine enantiomers in dogs, rats, and humans receiving venlafaxine
Chirality 1992;4(2):84-90.PMID:1616828DOI:10.1002/chir.530040204.
A stereospecific high-performance liquid chromatographic (HPLC) method was developed for the quantitation of the enantiomers of venlafaxine, an antidepressant, in dog, rat, and human plasma. The procedure involves derivatization of venlafaxine with the chiral reagent, (+)-S-naproxen chloride, and a postderivatization procedure. The method was linear in the range of 50 to 5,000 ng of each enantiomer per ml of plasma. No interference by endogenous substances or known metabolites of venlafaxine occurred. Studies to characterize the disposition of the enantiomers of venlafaxine were conducted in dog, rat, and human, following oral administration of venlafaxine. The Cmax, area under the curve (AUC) and (S)/(R) concentration ratios of the (R)- and (S)-enantiomers were compared. In rats, the mean plasma ratio of (S)-Venlafaxine to that of (R)-venlafaxine over 0.5 to 6.0 h varied from 2.97 to 8.50 with a mean value of 5.51 +/- 2.45. The Cmax, AUC0-infinity, and t 1/2 values of the (R)- and (S)-enantiomers in dogs were not significantly different from one another (P greater than 0.1). The mean ratios [(S)/(R)] of enantiomers of venlafaxine in human over a 2 to 6 h interval ranged from 1.33 to 1.35 with an overall ratio of 1.34 +/- 0.26 (n = 12). These ratios of the enantiomers [(S)/(R)] were not statistically different from unity (P greater than 0.1) indicating that the disposition of venlafaxine enantiomers in humans is not stereoselective and is more similar to that in dogs than that in rats.
Role of CYP2D6 in the stereoselective disposition of venlafaxine in humans
Pharmacogenetics 2003 Jan;13(1):39-47.PMID:12544511DOI:10.1097/00008571-200301000-00006.
CYP2D6 is involved in the O-demethylation metabolic pathway of venlafaxine in humans. In this study, we investigated whether this isozyme is stereoselective. Plasma samples from seven CYP2D6 extensive metabolizers (EMs) and five CYP2D6 poor metabolizers (PMs), collected during a period without and with coadministration of quinidine, were analysed. Subjects were administered venlafaxine hydrochloride 18.75 mg orally every 12 h for 48 h on two occasions (1 week apart); once alone and once during the concomitant administration of quinidine sulphate every 12 h. Blood and urine samples were collected under steady-state conditions over one dosing interval (12 h). The present results show that, although CYP2D6 catalyses the O-demethylation of both enantiomers of venlafaxine, it displays a marked stereoselectivity towards the (R)-enantiomer. The oral clearance of (R)-venlafaxine was found to be nine-fold higher in EMs compared to PMs [median (range) 173 (29-611) l/h versus 20 (16-24) l/h, P < 0.005], while it was two-fold higher for (S)-Venlafaxine [73 (32-130) l/h versus 37 (21-44) l/h, P < 0.05]. In EMs, quinidine decreased (R)- and (S)-Venlafaxine oral clearance by 12-fold ( 0.05) and four-fold ( 0.05), respectively. In contrast, quinidine did not have any effects on renal clearance of (R)-venlafaxine [4 (2-10) l/h for venlafaxine alone versus 5 (0.6-7) l/h for venlafaxine + quinidine] and of (S)-Venlafaxine [4 (1-7) l/h for venlafaxine alone versus 3 (0.4-6) l/h for venlafaxine + quinidine]. The coadministration of quinidine to EMs resulted in an almost complete inhibition of the partial metabolic clearance of (R)-venlafaxine to O-demethylated metabolites [127 (10-493) l/h down to 1 (0.1-3) l/h, 0.05], while a seven-fold reduction was measured for (S)-Venlafaxine [47 (14-94) l/h versus 7 (1-19) l/h, 0.05]. In PMs, coadministration of quinidine did not significantly change oral clearance and partial metabolic clearance of (R)- and (S)-Venlafaxine to its various metabolites. In contrast, data obtained on the partial metabolic clearance of (R)- and (S)-Venlafaxine to N-demethylated metabolites, a reaction which is mediated by CYP3A4, suggest a lack of stereoselectivity of this enzyme.
β-cyclodextrin improve the tolerant of freshwater algal Spiny Scenedesmus to chiral drugs venlafaxine and its metabolite
J Hazard Mater 2020 Nov 15;399:123076.PMID:32540709DOI:10.1016/j.jhazmat.2020.123076.
This study based on the freshwater algae Spiny scenedesmus (S. scenedesmus) with tolerance to venlafaxine aiming to investigate algae removal abilities. Here presented for the first time to evaluate the effect of β-cyclodextrin (β-CD) on reduce toxicity and enhance removal ability of venlafaxine and O-desmethylvenlafaxine to S. scenedesmus. Based on dose-response results, the toxicity of R-venlafaxine (EC50 = 6.81 mg·L -1) and R-O-desmethylvenlafaxine (EC50 = 3.36 mg·L -1) to algae were more than two times than those in the presence of β-CD treatment (10.64 mg L -1 for R-venlafaxine and 11.87 mg L -1 for R-O-desmethylvenlafaxine). The significant differences were observed between S-venlafaxine (11.07 mg L -1) and S-O-desmethylvenlafaxine (10.24 mg L -1), which were more toxic than R-forms. The half-lives of R- and S-venlafaxine were 0.8 d and 0.5 d in the presence of β-CD, which were obvious shorter than those in alone treatments. In addition, our experiments not only demonstrated that β-CD performed particularly well for removal of venlafaxine and O-desmethylvenlafaxine, it significantly reduces the toxicity of venlafaxine to alga. These results highlight advantages of β-CD relevant to chiral drugs removal and protection of aquatic organisms, which may have a better application for environmental and ecological safety in future.