(±)-Baclofen
(Synonyms: 巴氯芬) 目录号 : GC12927
(±)-Baclofen是γ-氨基丁酸（GABA）的亲脂性衍生物，是一种口服有效，选择性的代谢型GABAB受体激动剂，IC50为200nM。
Cas No.:1134-47-0
Sample solution is provided at 25 µL, 10mM.
(±)-Baclofen is a lipophilic derivative of γ-aminobutyric acid (GABA), and it is an orally effective and selective agonist of the metabotropic GABAB receptor with an IC50 of 200nM [1-2]. GABA is an inhibitory neurotransmitter that functions through heteromeric ligand-gated ion channels GABAA and GABAC as well as G protein-coupled receptors GABAB [3]. (±)-Baclofen can be used as a relaxant for muscle spasms and a central nervous system inhibitor [4].
In vitro, (±)-Baclofen (25, 50, and 100μM; 24, 48, 72, and 96h) inhibited the proliferation of HepG2 cells in a dose-dependent manner, downregulated intracellular cAMP levels, and upregulated the expression and phosphorylation of p21WAF1 protein. (±)-Baclofen also caused cell cycle arrest in the G0/G1 phase without inducing cell death [3]. (±)-Baclofen (1, 10μM; 24h) significantly reduced the activity of lactate dehydrogenase (LDH) in high-density model (HD) striatal cells (HD19 and HD43), enhanced the activity of cathepsin-like proteasome in the cells and cell viability [5].
In vivo, 30 minutes before behavioral tests, intraperitoneal injection of (±)-Baclofen (0.5, 1.5, and 2.5mg/kg/d; single-dose) enhanced the alcohol consumption behavior of mice in the Vogel conflict test, which might be due to the analgesic effect of Baclofen. Mice treated with (±)-Baclofen showed similar sedative effects in other tests (i.e., reduced activity) [6]. (±)-Baclofen (4mg/kg/d; 4d; i.p.) reversed the increase in the frequency of voluntary mouth-chewing movements (VCM) induced by reserpine in mice. After repeated treatment, (±)-Baclofen reduced the spontaneous systemic activity in mice induced by reserpine. [7].
References:
[1] Lin F, Cao Z, Hosford D A. Increased number of GABAB receptors in the lethargic (lh/lh) mouse model of absence epilepsy[J]. Brain research, 1993, 608(1): 101-106.
[2] Farokhnia M, Deschaine SL, Sadighi A, et al. A deeper insight into how GABA-B receptor agonism via baclofen may affect alcohol seeking and consumption: lessons learned from a human laboratory investigation. Mol Psychiatry. 2021;26(2):545-555.
[3] Wang T, Huang W, Chen F. Baclofen, a GABAB receptor agonist, inhibits human hepatocellular carcinoma cell growth in vitro and in vivo. Life Sci. 2008;82(9-10):536-541.
[4] DeFalco A P. Neuromuscular blocking agents and skeletal muscle relaxants[M]//Side Effects of Drugs Annual. Elsevier, 2024, 46: 171-180.
[5] Kim W, Seo H. Baclofen, a GABAB receptor agonist, enhances ubiquitin-proteasome system functioning and neuronal survival in Huntington's disease model mice. Biochem Biophys Res Commun. 2014;443(2):706-711.
[6] Li X, Risbrough VB, Cates-Gatto C, et al. Comparison of the effects of the GABAB receptor positive modulator BHF177 and the GABAB receptor agonist baclofen on anxiety-like behavior, learning, and memory in mice. Neuropharmacology. 2013; 70:156-167.
[7] Castro JP, Frussa-Filho R, Fukushiro DF, et al. Effects of baclofen on reserpine-induced vacuous chewing movements in mice. Brain Res Bull. 2006;68(6):436-441.
(±)-Baclofen是γ-氨基丁酸（GABA）的亲脂性衍生物，是一种口服有效，选择性的代谢型GABAB受体激动剂，IC50为200nM [1-2]。GABA是一种抑制性神经递质，通过异构配体门控离子通道GABAA和GABAC以及G蛋白连接接受器GABAB发挥作用 [3]。(±)-Baclofen可被用作肌肉痉挛的弛缓药和中枢神经系统抑制剂 [4]。
在体外，(±)-Baclofen（25、50和100μM; 24、48、72和96h）以剂量依赖性方式抑制了HepG2细胞的增殖，下调了细胞内cAMP水平并上调p21WAF1蛋白的表达以及磷酸化水平。(±)-Baclofen还导致细胞周期在G0/G1期停止，而不诱导细胞死亡 [3]。(±)-Baclofen（1，10μM；24h）显著降低了高密度模型（HD）纹状细胞（HD19和HD43）中乳酸脱氢酶（LDH）的活性，增强了细胞中类趋化胰蛋白酶样蛋白酶体活性和细胞活力 [5]。
在体内，行为测试前30分钟(±)-Baclofen（0.5, 1.5, and 2.5mg/kg/d; Single-dose）腹腔注射治疗加强了小鼠在Vogel冲突测试中的饮酒行为，这种现象可能是由于(±)-Baclofen的镇痛作用所致。接受(±)-Baclofen治疗的小鼠在其他测试中表现出类似镇静的效果（即活动减少）[6]。(±)-Baclofen（4mg/kg/d; 4d; i.p.）逆转了利血平诱导的小鼠空口咀嚼运动（VCM）频率的增加，在重复治疗后，(±)-Baclofen减少了利血平诱导的小鼠自发性的全身性活动 [7]。
| Cell experiment [1]: | |
Cell lines | HepG2 cells |
Preparation Method | HepG2 cells were seeded into 96-well plates (10,000 per well) in a final volume of 200μl medium. After a 24-hour attachment, cells were incubated with (±)-Baclofen (25, 50 and 100μM) in the absence or presence of Pha (100μM) for indicated time intervals. During this time, the culture medium was replaced with fresh medium every 24h. After treatment, cell proliferation was evaluated by 3-(4, 5-dimethylthiazol-2-yl)5-(3-carboxymethoxyphenyl)2-(4-sulfophenyl)2H-tetrazolium, inner salt (MTS) assay. The OD values were measured at 490nm with a microplate spectrophotometer (Molecular Devices). |
Reaction Conditions | 25, 50 and 100μM; 24, 48, 72, and 96h |
Applications | (±)-Baclofen inhibited the proliferation of HepG2 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | C57BL/6J mice |
Preparation Method | (±)-Baclofen was dissolved in sterile 0.9% saline and injected intraperitoneally (i.p.) 30min before testing. BHF177 was suspended in 0.5% methylcellulose and administered orally (p.o.) 60min before testing. The convulsant drug PTZ was dissolved in sterile 0.9% saline and injected i.p. immediately before testing. The doses of (±)-Baclofen (0.5, 1.5, and 2.5mg/kg) and route of administration (i.p.) were chosen based on previously published studies that all reported a narrow effective dose range of this compound before sedative effects were manifested. The doses of BHF177 (10, 20, and 40mg/kg) and route of administration (p.o.) were also chosen based on previous studies. All of the drugs were administered in volumes of 0.1ml/10g body weight in mice. The effects of (±)-baclofen and BHF177 were studied by using the "between-group design". Behavioral tests were designed, and the sample size for each group was 12. |
Dosage form | 0.5, 1.5, and 2.5mg/kg/d; Single-dose; i.p. |
Applications | (±)-Baclofen treatment increased the alcohol consumption behavior of mice in the Vogel conflict test. This phenomenon might be due to the analgesic effect of (±)-Baclofen. Mice treated with (±)-Baclofen also showed similar sedative effects in other tests (i.e., reduced activity). |
References: | |
| Cas No. | 1134-47-0 | SDF | |
| 别名 | 巴氯芬 | ||
| 化学名 | β-(aminomethyl)-4-chloro-benzenepropanoic acid | ||
| Canonical SMILES | ClC1=CC=C(C(CN)CC(O)=O)C=C1 | ||
| 分子式 | C10H12ClNO2 | 分子量 | 213.7 |
| 溶解度 | 0.1 M HCl : 10 mg/mL (46.80 mM; Need ultrasonic); DMSO : 4.81 mg/mL (22.51 mM; ultrasonic and warming and adjust pH to 4 with HCl and heat to 60°C); H2O : 2 mg/mL (9.36 mM; Need ultrasonic) | 储存条件 | Store at 2-8°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.6795 mL | 23.3973 mL | 46.7946 mL |
| 5 mM | 935.9 μL | 4.6795 mL | 9.3589 mL |
| 10 mM | 467.9 μL | 2.3397 mL | 4.6795 mL |
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