Radafaxine hydrochloride (GW-353162A)
(Synonyms: 盐酸安非他酮吗啉代杂质,GW-353162A; BW-306U) 目录号 : GC31060
An active metabolite of bupropion
Cas No.:106083-71-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
S,S-hydroxy Bupropion is an active metabolite of the antidepressant bupropion.1,2 It is formed from bupropion by the cytochrome P450 (CYP) isoform CYP2B6.3 S,S-hydroxy Bupropion inhibits dopamine and norepinephrine but not serotonin (5-HT) reuptake in HEK293 cells expressing the human transporters (IC50s = 0.63, 0.241, and >100 ?M, respectively).1 It is also an antagonist of α3β4-, α4β2-, α4β4-, and α1β1 subunit-containing nicotinic acetylcholine receptors (nAChRs; IC50s = 11, 3.3, 30, and 28 ?M, respectively). S,S-hydroxy Bupropion inhibits nicotine-induced analgesia in the tail-flick and hot plate tests, hyperlocomotion, and hypothermia in mice (ED50s = 0.2, 1, 0.9, and 1.5 mg/kg, respectively). It substitutes for (+)-amphetamine in rats in a two-lever drug discrimination test (ED50 = 4.4 mg/kg).2
1.Lukas, R.J., Muresan, A.Z., Damaj, M.I., et al.Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: Aids to smoking cessationJ. Med. Chem.53(12)4731-4748(2010) 2.Bondarev, M.L., Bondareva, T.S., Young, R., et al.Behavioral and biochemical investigations of bupropion metabolitesEur. J. Pharmacol.474(1)85-93(2003) 3.Coles, R., and Kharasch, E.D.Stereoselective metabolism of bupropion by cytochrome P4502B6 (CYP2B6) and human liver microsomesPharm. Res.25(6)1405-1411(2008)
| Cas No. | 106083-71-0 | SDF | |
| 别名 | 盐酸安非他酮吗啉代杂质,GW-353162A; BW-306U | ||
| Canonical SMILES | O[C@]1(C2=CC=CC(Cl)=C2)[C@H](C)NC(C)(C)CO1.[H]Cl | ||
| 分子式 | C13H19Cl2NO2 | 分子量 | 292.2 |
| 溶解度 | DMSO : ≥ 38 mg/mL (130.05 mM) | 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 | 3.4223 mL | 17.1116 mL | 34.2231 mL |
| 5 mM | 0.6845 mL | 3.4223 mL | 6.8446 mL |
| 10 mM | 0.3422 mL | 1.7112 mL | 3.4223 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。
The slow and long-lasting blockade of dopamine transporters in human brain induced by the new antidepressant drug radafaxine predict poor reinforcing effects
Background: (2S,3S)-2-(3-Chlorophenyl)-3,5,5,-trimethyl-2-morpholinol hydrochloride (radafaxine) is a new antidepressant that blocks dopamine transporters (DAT). A concern with drugs that block (DAT) is their potential reinforcing effects and abuse liability. Using positron emission tomography (PET) we have shown that for DAT-blocking drugs to produce reinforcing effects they must induce >50% DAT blockade and the blockade has to be fast (within 15 minutes). This study measures the potency and kinetics for DAT blockade by radafaxine in human brain. Methods: PET and [11C]cocaine were used to estimate DAT blockade at 1, 4, 8, and 24 hours after radafaxine (40 mg p.o.) in 8 controls. Plasma pharmacokinetics and behavioral and cardiovascular effects were measured in parallel. Results: DAT blockade by radafaxine was slow, and at 1 hour, it was 11%. Peak blockade occurred at about 4 hours and was 22%. Blockade was long lasting: at 8 hours 17%, and at 24 hours 15%. Peak plasma concentration occurred about 4 to 8 hours. No behavioral or cardiovascular effects were observed. Conclusions: The relatively low potency of radafaxine in blocking DAT and its slow blockade suggests that it is unlikely to have reinforcing effects. This is consistent with preclinical studies showing no self-administration. This is the first utilization of PET to predict abuse liability of a new antidepressant in humans based on DAT occupancy and pharmacokinetics.
Pharmacokinetics of bupropion and metabolites in plasma and brain of rats, mice, and guinea pigs
Drug Metab Dispos.1986 Nov-Dec;14(6):692-7.PMID: 2877828DOI:
Recent reports indicate that bupropion, a novel non-tricyclic antidepressant, is metabolized differently in certain species of animals. To further define the disposition of bupropion, a study was done involving three species, the rat, mouse, and guinea pig, as animal models to evaluate bupropion metabolism. The pharmacokinetic profiles of bupropion and its major basic metabolites, BW 306U and BW A494U, were determined following the ip administration of 40 mg/kg bupropion to these animals. Pharmacokinetic profiles of the parent drug and metabolites from plasma and brain samples were obtained using a liquid chromatographic procedure. Further investigation of the reduced bupropion metabolite BW A494U was carried out by the ip administration of this metabolite to these animals and assaying the plasma and brain samples 90 min after dosing. Analysis of the pharmacokinetic data revealed that the rat quickly metabolized bupropion, but no basic metabolites accumulated. The mouse metabolized bupropion predominantly to BW 306U, whereas the guinea pig converted bupropion to reduced bupropion (BW A494U) as well as BW 306U. Brain/plasma ratios of bupropion among these animals did not vary significantly. However, both metabolites showed dramatic differences in their brain/plasma ratios among these species. When reduced bupropion (BW A494U) was injected, almost 3% of the plasma concentration of BW A494U was determined to be bupropion in the rat. Lesser amounts were converted in the mouse and guinea pig. Therefore, we have demonstrated that distinct differences exist in the metabolism of bupropion in various species of animals. The guinea pig, when compared to the rat or mouse, appears to constitute a model that most closely resembles that of human bupropion metabolism.
Pharmacological significance of the species differences in bupropion metabolism
Xenobiotica.1987 Mar;17(3):287-98.PMID: 3107223DOI:10.3109/00498258709043939.
Bupropion provided a dose-dependent prevention of tetrabenazine-induced sedation in mice but not rats. Bupropion was extensively metabolized in mice, rats, dogs and man. About 85% of the dose was excreted in urine of rats and man. The predominant metabolites in rat urine were side chain cleavage products of bupropion (m-chlorobenzoic acid) with a minor fraction consisting of basic side chain hydroxylated metabolites. Mice, dogs and man form a major side chain hydroxylated product (BW 306U) which appeared in higher concentration than bupropion in plasma of these species but not rats. The relatively high plasma levels of BW 306U in mice but not rats may account for the species difference in pharmacological response observed with bupropion.
Brain regional [3H]flunitrazepam binding in rats chronically treated with bupropion or B.W.306U
Brain Res.1986 Mar 5;367(1-2):385-9.PMID: 3084038DOI:10.1016/0006-8993(86)91624-0.
After 21 days of twice daily i.p. injections of bupropion (10 mg/kg), B.W.306U (10 mg/kg) or saline, 5 rat brain regions were removed for [3H]flunitrazepam binding assay. Scatchard analysis of the binding data revealed no change in the Bmax in any brain regions in drug-treated rats compared to controls. There was, however, a significant change in the Kd value in the limbic forebrain of B.W.306U-treated rats.