BQCA
(Synonyms: 1-(4-甲氧基苄基)-4-氧代-1,4-二氢喹啉-3-羧酸) 目录号 : GC15758
A positive allosteric modulator of the M1 mAChR
Cas No.:338747-41-4
Sample solution is provided at 25 µL, 10mM.
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Benzyl Quinolone Carboxylic Acid (BQCA) is a highly selective allosteric potentiator of the M1 muscarinic acetylcholine receptor (mAChR) [1].
M1 is most abundantly mAChR expressed in the hippocampus, cortex, and striatum, and localizes to postsynaptic membranes. M1 regulates several ion channels such as KCNQ inwardly rectifying K+currents, voltage-gated calcium channels, and NMDA receptors. M1 mediates the cognitive effects of ACh. M1 activation could slow AD progression by reducing Aβ42 peptides [1].
In vitro: BQCA alone showed no effect on calcium mobilization up to 10 μM but increased ACh potency 128.8 ± 20.1-fold at 100 μM. In CHO cells stably expressing human M1, BQCA (100 μM) activated M1 in the absence of ACh to an approximate 50% maximal response. BQCA had no effect on M2–M5, indicating 100-fold selectivity [1]. BQCA dose-dependently reduced the concentration of acetylcholine required to activate the M1 receptor [1]. The effective range for potentiation of M1 in cells by BQCA was 0.1 to 100 μM, with an inflection point value of 845 nM when 3 nM acetylcholine was used [1].
In vivo: In wild-type mice, BQCA (15 mg/kg) induced c-fos and arc RNA in the cortex, hippocampus, and cerebellum and the arc was also elevated in the striatum. BQCA had no effect in M1-/- mice. In wild-type mice, oral administration of 15 mg/kg BQCA increased the ratio of phosphoERK (pERK) to total ERK by 28%. BQCA showed excellent brain penetration and increased the firing rate of medial prefrontal cortex neurons in vivo in rats [2].
References:
[1] Ma L, Seager M A, Wittmann M, et al. Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation[J]. Proceedings of the National Academy of Sciences, 2009, 106(37): 15950-15955.
[2] Shirey J K, Brady A E, Jones P J, et al. A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning[J]. Journal of Neuroscience, 2009, 29(45): 14271-14286.
Kinase experiment: | Competition binding reactions used 25 μg human M1 CHO membrane protein, BQCA or vehicle, and 0.15 nM [3H]NMS in 96-well deep-well plates. Binding reactions (30 °C for 2-3 h) are terminated by rapid filtration. Nonspecific binding is determined by adding 10 μM atropine. Filter plates are ished 4×with ice-cold 20 mM HEPES, 100 mM NaCl, and 5 mM MgCl2, pH 7.4 using a 96-well harvester. Plates are dried and radioactivity counted with a microplate scintillation counter[1]. |
Animal experiment: | Rats: Male Sprague-Dawley rats weighing 225-250 g, are injected i.p. with the micro-suspension (containing 10% tween 80) of BQCA at the dose of 10 mg/kg. The blood and whole brain tissue samples are collected at 0.5, 1, 2, 4 and 8 h. Blood samples are collected through cardiac puncture in EDTA vacutainer tubes. The plasma is separated by centrifugation and stored at −80°C until analysis. The animals are decapitated and the whole brain tissue are removed and immediately frozen on dry ice[2]. Mice: Mice are dosed I.P. with BQCA in 5% beta-cyclodextrin and/or 0.3 mg/kg scopolamine in 0.9% saline 30 min before placement into a chamber for 2 min before 2 tone-footshock pairings (3 kHz, 85 dB tone for 30 s co-terminated with a 0.5 mA, 1 s shock) 2 min apart. Mice are removed to their home cage 30 s after the last pairing. Twenty-four hours later mice are placed into the same chamber and freezing is measured by Video Freeze[1]. |
References: [1]. Ma L, et al. Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15950-5. | |
| Cas No. | 338747-41-4 | SDF | |
| 别名 | 1-(4-甲氧基苄基)-4-氧代-1,4-二氢喹啉-3-羧酸 | ||
| 化学名 | 1,4-dihydro-1-[(4-methoxyphenyl)methyl]-4-oxo-3-quinolinecarboxylic acid | ||
| Canonical SMILES | COC1=CC=C(CN2C(C=CC=C3)=C3C(C(C(O)=O)=C2)=O)C=C1 | ||
| 分子式 | C18H15NO4 | 分子量 | 309.3 |
| 溶解度 | ≥ 30.9mg/mL in DMSO with gentle warming | 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 | 3.2331 mL | 16.1655 mL | 32.3311 mL |
| 5 mM | 0.6466 mL | 3.2331 mL | 6.4662 mL |
| 10 mM | 0.3233 mL | 1.6166 mL | 3.2331 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。
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Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet