Home>>Signaling Pathways>> Neuroscience>> 5-HT Receptor>>Wf-516

Wf-516 Sale

目录号 : GC31041

Wf-516是一种5-HTreuptake的抑制剂,同时为5-HT1A和5-HT2A受体拮抗剂,对人体5-HT1A和5-HT2A受体的Ki值分别为5nM和40nM,具有抗抑郁作用。

Wf-516 Chemical Structure

Cas No.:310392-94-0

规格 价格 库存 购买数量
1mg
¥10,799.00
现货
5mg
¥21,599.00
现货
10mg
¥37,842.00
现货
20mg
¥66,134.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Animal experiment:

A series of 6 and 5 dynamic PET scans is performed for each rat approximately 5 h and 30 min after oral and intraperitoneal pretreatments with graded doses of Wf-516 (vehicle only, 1, 3, 10, 30 and 100 mg/kg) and pindolol (vehicle only, 1, 3, 10 and 30 mg/kg), respectively. Scans for the same individual rat receiving Wf-516 (n = 4) and pindolol (n = 3) are conducted more than 2 weeks and 1 week apart, respectively. PET imaging is also carried out for rats receiving oral administration of 30 mg/kg fluvoxamine dissolved in 0.5%HPMC 30 min before pindolol treatment in order to investigate the effects of fluvoxamine-induced increase of endogenous 5-HTs on the measurements of 5-HT1A receptor occupancies.

References:

[1]. El Mansari M, et al. In vivo electrophysiological assessment of the putative antidepressant Wf-516 in the rat raphe dorsalis, locus coeruleus and hippocampus. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):351-61. Epub 2007 Nov 30.
[2]. Saijo T, et al. Presynaptic selectivity of a ligand for serotonin 1A receptors revealed by in vivo PET assays of rat brain. PLoS One. 2012;7(8):e42589.

产品描述

Wf-516 is an inhibitor of 5-HT reuptake, and an antagonist of 5-HT1A and 5-HT2A receptors, with Ki of 5 nM and 40 nM for 5-HT1A receptor and 5-HT2A receptor in humans, respectively, and has potent antidepressant activity.

Wf-516 shows high affinity for 5-HT1A receptors in the hippocampus and raphe nucleus of rats with Ki of 8.1 nM and 7.9 nM, respectively[2].

Wf-516 (0.5 mg/kg, i.v.) does not induce any change in the firing activity of 5-HT neurons, but significantly blocks the inhibitory effect of 8-OHDPAT (a 5-HT autoreceptor agonist) by 70%. A full dose-response relationship between the suppression of DRN firing activity and different doses of LSD shows a significant fourfold shift to the right in the Wf-516 pretreated rats (ED50 = 32.4 ± 1.0 μg/kg) as compared to controls (ED50 = 7.5 ± 1.2 μg/kg). After intravenous administration of successive doses of 1.25 mg/kg of Wf-516 (up to 10 mg/kg), the effect of microiontophoretically applied 5-HT is prolonged and reaches statistical significance at 7.5 mg/kg. At this dose, the RT50 value is increased by 53% and, by 75% at the highest dose of 10 mg/kg of Wf-516 used[1]. Oral administration of 30 mg/kg Wf-516 to these 5,7-DHT-treated rats induces a significant decrease of BPND in the hippocampus as compared with baseline, but no additional reduction of BPND is observed in the raphe nucleus. Oral ED50 values for Wf-516 in the hippocampus and raphe nucleus are 5.3 mg/kg and 4.2 mg/kg, respectively[2].

[1]. El Mansari M, et al. In vivo electrophysiological assessment of the putative antidepressant Wf-516 in the rat raphe dorsalis, locus coeruleus and hippocampus. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):351-61. Epub 2007 Nov 30. [2]. Saijo T, et al. Presynaptic selectivity of a ligand for serotonin 1A receptors revealed by in vivo PET assays of rat brain. PLoS One. 2012;7(8):e42589.

Chemical Properties

Cas No. 310392-94-0 SDF
Canonical SMILES O[C@H](COC1=C2C=C(C3=NN=C(C)O3)OC2=CC=C1)CN(CC4)CCC4C5=CC=C(Cl)C(Cl)=C5
分子式 C25H25Cl2N3O4 分子量 502.39
溶解度 Soluble in DMSO 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。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 1.9905 mL 9.9524 mL 19.9049 mL
5 mM 0.3981 mL 1.9905 mL 3.981 mL
10 mM 0.199 mL 0.9952 mL 1.9905 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

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
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

Research Update

In vivo electrophysiological assessment of the putative antidepressant Wf-516 in the rat raphe dorsalis, locus coeruleus and hippocampus

Wf-516 is a potential novel antidepressant. It has high affinity for serotonin (5-hydroxytryptamine; 5-HT) transporters, 5-HT(1A) and 5-HT(2A) receptors. In the present study, the pharmacologic properties of Wf-516 were thus assessed using in vivo electrophysiology in the rat dorsal raphe nucleus (DRN), locus coeruleus (LC) and hippocampus. Glass microelectrodes were lowered into the DRN, LC or hippocampus, and neurons were recorded and tested using systemic or microiontophoretic injections of drugs. In the DRN, cumulative doses of 0.5 mg/kg of Wf-516 were injected intravenously and total inhibition of 5-HT neurons firing was obtained with 2.8 +/- 0.3 mg/kg. The administration of 1 mg/kg of Wf-516, which by itself did not induce a change in the firing of 5-HT neurons, markedly attenuated the inhibitory effect of the 5-HT(1A) autoreceptor agonist LSD, indicating that Wf-516 is a 5-HT(1A) autoreceptor antagonist. In the LC, 1 mg/kg of Wf-516 dampened the inhibitory effect of the preferential 5-HT(2A) agonist DOI on norepinephrine (NE) neurons, indicating that Wf-516 is also a 5-HT(2A) receptor antagonist. In the hippocampus, cumulative intravenous doses of Wf-516 significantly increased the recovery time of firing activity of CA(3) pyramidal neurons after 5-HT applications, indicating an inhibitory effect on 5-HT reuptake. Unlike the 5-HT(1A) antagonist WAY100635, Wf-516 did not block the inhibitory effect of microiontophoretic application of 5-HT, indicating that this drug is devoid of 5-HT(1A) receptor antagonistic activity in this postsynaptic structure. These properties of WF-516 define the transporter/receptorial profile of an antidepressant with superior effectiveness.

Presynaptic selectivity of a ligand for serotonin 1A receptors revealed by in vivo PET assays of rat brain

A novel investigational antidepressant with high affinity for the serotonin transporter and the serotonin 1A (5-HT(1A)) receptor, called Wf-516 (structural formula: (2S)-1-[4-(3,4-dichlorophenyl)piperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride), has been found to exert a rapid therapeutic effect, although the mechanistic basis for this potential advantage remains undetermined. We comparatively investigated the pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission tomographic (PET) and autoradiographic assays of rat brains in order to elucidate their molecular interactions with presynaptic and postsynaptic 5-HT(1A) receptors. In contrast to the full receptor occupancy by pindolol in PET measurements, the binding of Wf-516 to 5-HT(1A) receptors displayed limited capacity, with relatively high receptor occupancy being achieved in regions predominantly containing presynaptic receptors. This selectivity was further proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5-HT(1A) receptors. In addition, [(35)S]guanosine 5'-O-[γ-thio]triphosphate autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT(1A) receptors. This finding has lent support to reports that diverse partial agonists for 5-HT(1A) receptors exert high sensitivity for presynaptic components. Thus, the present PET data suggest a relatively high capacity of presynaptic binding sites for partial agonists. Since our in vitro and ex vivo autoradiographies failed to illustrate these distinct features of Wf-516, in vivo PET imaging is considered to be, thus far, the sole method capable of pharmacokinetically demonstrating the unique actions of Wf-516 and similar new-generation antidepressants.

Utility of small-animal positron emission tomographic imaging of rats for preclinical development of drugs acting on the serotonin transporter

Visualization of neurotransmission components in living small animals using positron emission tomography (PET) has the potential of contributing to the preclinical development of neuroactive drugs, although it is yet to be examined whether quantitative animal PET data on candidate compounds can be extrapolated to humans. Here, we investigated the comparability of the occupancies of serotonin transporter (5-HTT) by therapeutic agents in rat PET studies with our predetermined data from ex- vivo animal experiments and clinical PET scans. Rats were treated with varying doses of fluvoxamine and a newly developed compound, (2S)-1-[4-(3,4-dichlorophenyl) piperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride (Wf-516), and underwent PET scans with [11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([11C]DASB), a selective radioligand for in-vivo quantification of 5-HTT. PET images indicated a reduction of [11C]DASB binding to 5-HTT as a function of the doses and/or plasma concentrations of fluvoxamine and Wf-516. The doses of these drugs at half-maximal effect (15.2 mg/kg and 3.1 mg/kg, respectively), determined that using binding potentials for [11C]DASB, were comparable to those estimated by our previous ex-vivo measurements in rats (4.5 mg/kg and 1.1 mg/kg, respectively), as there was only a 3-fold difference between these results. Moreover, the plasma concentration of fluvoxamine needed for 50% occupancy of central 5-HTT (6.1 ng/ml) was almost equivalent to the value determined in human PET studies (4.6 ng/ml). These findings support the view that the conjunctive use of small-animal PET and [11C]DASB facilitates a quantitative comparison of in-development drugs targeting 5-HTT with established inhibitors and a predictive estimation of their plasma concentrations exerting therapeutic effects in humans.