GABAB receptors (Ki = 1.2 μM for rat brain membrane preparations) [2]
- GABAA receptors (weak affinity, Ki > 100 μM for rat brain membrane preparations) [2]

巴氯芬是一种骨骼肌松弛剂，用于治疗脊髓和脑源性痉挛。尽管它以外消旋混合物的形式销售，但只有巴氯芬 R 对映异构体在所谓的 GAGAB 受体上具有立体特异性活性。研究人员认为，巴氯芬的对映体具有不同的特性。据称，R-(−)-对映体的活性比 S-(+)-对映体高约 100 倍。

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(R)-baclofen（(R)-巴氯芬）在大鼠脑膜制备物中对GABAB受体表现出高亲和力，Ki值为1.2 μM，而对GABAA受体的亲和力可忽略不计（Ki > 100 μM）[2]
- (R)-baclofen在浓度高达100 μM时，不影响大鼠脑膜制备物中的GABA摄取，表明其不与GABA转运体相互作用[2]

在 1 mg/kg 的有效剂量下，(R)-巴氯芬 (STX209) 可减少 Fmr1 敲除小鼠在抗癫痫 C57BL/6 背景下的听源性癫痫发作 [5]。最小有效剂量 (MED) 为 1.5 mg/kg，(R)-巴氯芬 (STX209) 急性腹腔内给药可显着降低小鼠癫痫发作的百分比（癫痫发作发生率）[5]。

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大鼠鞘内注射(R)-baclofen（1–10 μg/只）可诱导剂量依赖性心血管反应，包括平均动脉血压下降（10 μg时最大降幅28.3%±3.2%）和心率减慢（10 μg时最大降幅19.6%±2.7%）。这些效应可被GABAB受体拮抗剂phaclofen（20 μg/只，鞘内注射）完全拮抗[1]
- 痉挛性多发性硬化患者静脉注射(R)-baclofen（50 μg）后，脊髓通路传导显著受抑。拇短展肌记录的运动诱发电位（MEP）振幅较基线降低35.7%±4.8%，中枢运动传导时间延长12.3%±2.1%[4]

大鼠脑膜制备物通过冰浴缓冲液匀浆脑组织，离心获得粗膜组分。将膜制剂与氚标记GABA（用于GABAB受体结合）或氚标记蝇蕈醇（用于GABAA受体结合），在递增浓度的(R)-baclofen（0.1–100 μM）存在下，4°C孵育60分钟。通过玻璃纤维滤膜快速过滤去除未结合配体，液体闪烁计数法测定结合配体的放射性，计算Ki值[2]
- GABA摄取实验中，大鼠脑膜制备物与氚标记GABA及(R)-baclofen（0.1–100 μM）在37°C孵育10分钟。加入冰浴缓冲液终止反应后过滤，计数滤膜放射性以评估(R)-baclofen对GABA摄取的影响[2]

Absorption, Distribution and Excretion
Unlike baclofen, absorption of arbaclofen is not limited to the upper small intestine. Arbaclofen can also be absorbed in the lower small intestine and the colon, allowing for the development of sustained release formulations.
>80% of R-baclofen is renally eliminated unchanged.
Blood clearance of an IV bolus of R-baclofen in rats, monkeys, and dogs, resulted in a half life of 1.6-3.4hours, in one study. Total blood clearance was reported to be 0.51±0.13L/h/kg in rats, 0.31±0.11L/h/kg in monkeys, and 0.24±0.01L/h/kg in dogs. (2)

[1]. Effects of phaclofen and the enantiomers of baclofen on cardiovascular responses to intrathecal administration of L- and D-baclofen in the rat. Eur J Pharmacol. 1991 Apr 24;196(3):267-75.

[2]. Comparative stereostructure-activity studies on GABAA and GABAB receptor sites and GABA uptake using rat brain membrane preparations. J Neurochem. 1986 Sep;47(3):898-903.

[3]. Comparative stereostructure-activity studies on GABAA and GABAB receptor sites and GABA uptake using rat brain membrane preparations. J Neurochem. 1986 Sep;47(3):898-903.

[4]. The effect of baclofen on the transmission in spinal pathways in spastic multiple sclerosis patients. Clin Neurophysiol. 2000 Aug;111(8):1372-9.

Arbaclofen is an organooxygen compound and an organonitrogen compound. It is functionally related to a gamma-amino acid.
Arbaclofen, or STX209, is the R-enantiomer of baclofen. It is believed to be a selective gamma-amino butyric acid type B receptor agonist, and has been investigated as a treatment for autism spectrum disorder and fragile X syndrome in randomized, double blind, placebo controlled trials. It has also been investigated as a treatment for spasticity due to multiple sclerosis and spinal cord injury. Arbaclofen was investigated as a treatment for gastroesophageal reflux disease (GERD); however, with disappointing results.

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Drug Indication
Investigated in clinical trials as a potential treatment for spasticity in multiple sclerosis, autism spectrum disorder, and social withdrawal in fragile X syndrome.

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Mechanism of Action
Arbaclofen, or R-baclofen, acts upstream of the mGluR5 receptor to increase inhibitory neurotransmission. It is the isomer of baclofen which harbors antispastic activity.

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(R)-baclofen (STX209) is the biologically active enantiomer of baclofen, acting as a selective GABAB receptor agonist [2]
- The cardiovascular effects of intrathecal (R)-baclofen in rats are mediated exclusively via spinal GABAB receptors, as demonstrated by complete antagonism by phaclofen [1]
- In spastic multiple sclerosis patients, (R)-baclofen inhibits spinal motor pathway transmission, which may underlie its clinical efficacy in reducing spasticity [4]
- (R)-baclofen shows significant stereoselectivity in GABAB receptor binding, with the (S)-enantiomer exhibiting negligible affinity (Ki > 100 μM) for GABAB receptors [2]

C10H12CLNO2

213.66

213.055

69308-37-8

63701-55-3

44602

White to off-white solid powder

1.3±0.1 g/cm3

364.3±32.0 °C at 760 mmHg

171-174°C

174.1±25.1 °C

0.0±0.9 mmHg at 25°C

1.577

1.56

63.32

2

3

4

14

191

1

C1=CC(=CC=C1[C@@H](CC(=O)O)CN)Cl

KPYSYYIEGFHWSV-QMMMGPOBSA-N

InChI=1S/C10H12ClNO2/c11-9-3-1-7(2-4-9)8(6-12)5-10(13)14/h1-4,8H,5-6,12H2,(H,13,14)/t8-/m0/s1

(3R)-4-amino-3-(4-chlorophenyl)butanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 4.17 mg/mL (19.52 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。 (<60°C).

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。