(+)-AJ 76 hydrochloride
目录号 : GC13156
(+)-AJ 76 hydrochloride是一种对突触前受体具有优先作用的多巴胺受体(dopamine receptors, DRs)拮抗剂(hD3、hD4、hD2S、hD2L和rD2受体的pKi值分别为6.95、6.67、6.37、6.21和6.07)。
Cas No.:85379-09-5
Sample solution is provided at 25 µL, 10mM.
(+)-AJ 76 hydrochloride is a dopamine receptors (DRs) antagonist [1] with preferential action at presynaptic receptors (pKi values are 6.95, 6.67, 6.37, 6.21 and 6.07 at hD3, hD4, hD2S, hD2L and rD2 receptors respectively). Dopamine is not only a neurotransmitter involved in motor, cognitive, and reward regulation, but it also plays an immunomodulatory role in the central and peripheral nervous systems[2]. (+)-AJ 76 hydrochloride can increase extracellular dopamine concentration by blocking presynaptic inhibitory receptors D2R and/or D3R on dopaminergic neuron terminals, which promotes dopamine transmission[3], and is therefore commonly used in neurology and studies of neurological related diseases such as Alzheimer's disease.
In vitro, (+)-AJ 76 hydrochloride (1μM) treatment of HEK 293 cells transfected with the D3 receptor for 35min reduced cellular phospholipase D (PLD) levels[4].
In vivo, MitoPark mice treated with intraperitoneal injection (+)-AJ 76 hydrochloride (20mg/kg) for 60 minutes significantly reduced the levels of DOPAC (3,4-Dihydroxyphenylacetic acid) in mouse cerebrospinal fluid and HVA (homovanillic acid) in mouse cerebrospinal fluid and plasma, suggesting that dopamine neuron challenge Test (DNC Test) using (+)-AJ 76 hydrochloride is helpful for early detection of PD (Parkinson’s disease)[5]. (+)-AJ 76 hydrochloride (300μmol/kg/day) fed to male Sprague-Dawley rats for 7 days increased voluntary activity activity and DOPAC levels in the striatum[6].
References:
[1] Svensson K, Johansson AM, Magnusson T, Carlsson A. (+)-AJ 76 and (+)-UH 232: central stimulants acting as preferential dopamine autoreceptor antagonists. Naunyn Schmiedebergs Arch Pharmacol. 1986 Nov;334(3):234-45. doi: 10.1007/BF00508777. PMID: 2880302.
[2] Channer, Breana et al. “Dopamine, Immunity, and Disease.” Pharmacological reviews vol. 75,1 (2023): 62-158. doi:10.1124/pharmrev.122.000618
[3] Waters N, Lagerkvist S, Löfberg L, Piercey M, Carlsson A. The dopamine D3 receptor and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH232; a microdialysis study. Eur J Pharmacol. 1993 Sep 28;242(2):151-63. doi: 10.1016/0014-2999(93)90075-s. PMID: 8253112.
[4] Everett PB, Senogles SE. D3 dopamine receptor activates phospholipase D through a pertussis toxin-insensitive pathway. Neurosci Lett. 2004 Nov 16;371(1):34-9. doi: 10.1016/j.neulet.2004.08.033. PMID: 15500962.
[5] Zhou, Jingheng et al. “AJ76 and UH232 as potential agents for diagnosing early-stage Parkinson's disease.” Neuropharmacology vol. 226 (2023): 109397. doi:10.1016/j.neuropharm.2022.109397
[6] Kullingsjö H, Carlsson A, Svensson K. Effects of repeated administration of the preferential dopamine autoreceptor antagonist, (+)-AJ76, on locomotor activity and brain DA metabolism in the rat. Eur J Pharmacol. 1991 Dec 3;205(3):241-6. doi: 10.1016/0014-2999(91)90904-5. PMID: 1817961.
(+)-AJ 76 hydrochloride是一种对突触前受体具有优先作用的多巴胺受体(dopamine receptors, DRs)拮抗剂(hD3、hD4、hD2S、hD2L和rD2受体的pKi值分别为6.95、6.67、6.37、6.21和6.07)[1]。多巴胺不仅是一种参与运动、认知和奖励调节的神经递质,它在中枢神经系统和外周神经系统也起免疫调节的作用[2]。而(+)-AJ 76 hydrochloride可以通过阻断多巴胺能神经元末梢上突触前抑制性受体D2R和 (或) D3R,使得细胞外多巴胺浓度升高, 促进多巴胺的传递[3],因此常用于神经学和阿尔兹海默症等神经相关疾病的研究。
在体外,(+)-AJ 76 hydrochloride(1μM)处理转染D3受体的HEK 293细胞35min,可降低细胞磷脂酶D(phospholipase D,PLD)的水平[4]。
在体内,(+)-AJ 76 hydrochloride(20mg/kg)腹腔注射处理MitoPark mice小鼠60分钟,显著降低了小鼠脑脊液中3,4-二羟基苯乙酸(3,4-Dihydroxyphenylacetic acid, DOPAC)和小鼠脑脊液和血浆中高香草酸(homovanillic acid, HVA)的水平,揭示使用(+)-AJ 76 hydrochloride的多巴胺神经元挑战试验(Dopamine Neuron Challenge Test, DNC Test)有助于帕金森病(Parkinson’s disease , PD)的早期检测[5]。(+)-AJ 76 hydrochloride(300μmol/kg/day)喂食雄性Sprague-Dawley大鼠7天,可以提高大鼠纹状体的自主活动活动和DOPAC水平[6]。
Cell experiment [1]: | |
Cell lines | HEK 293 cells |
Preparation Method | Firstly, transient transfection of human D3 receptor into HEK 293 cells, 24 hours post-transfection, HEK 293 cells were plated in 12-well cluster dishes and labeled with 10μCi/well (μCi is a unit of radioactive activity) of [3H]-myristic acid for 48h. Then added (+)-AJ 76 hydrochloride (1μM) for 5min. Finally, PLD (phospholipase D) activity was determined by the transphosphatidylation reaction in the presence of 1% ethanol and (+) 7-OH DPAT (a D3 receptor agonist) indicated for 30min at 37°C. |
Reaction Conditions | 1μM; 35min |
Applications | D3 receptor selective antagonists (+) 7-OH DPAT (a D3 receptor agonist) at a concentration of 1μM ablated D3 receptor-mediated PLD (phospholipase D) activity. |
Animal experiment [2]: | |
Animal models | MitoPark mice |
Preparation Method | The 20-week-old MitoPark mouse were injected with (+)-AJ 76 hydrochloride (20mg/kg) for 60min, then collected the CSF (cerebrospinal fluid) and plasma sample and compared the levels of DOPAC (3,4-Dihydroxyphenylacetic acid) and HVA (homovanillic acid) in CSF samples and the level of HVA in plasma samples between 20-week-old MitoPark mice and their littermate controls at the resting state. |
Dosage form | 20mg/kg for 60min; i.p. injection |
Applications | The levels of HVA in plasma samples of (+)-AJ 76 hydrochloride treated mice were decreased, as were the levels of HVA and DOPA in CSF sample, suggesting that the (+)-AJ 76 hydrochloride can detect Parkinson’s disease (PD) at an early stage. |
References: |
Cas No. | 85379-09-5 | SDF | |
化学名 | (1S,2R)-5-methoxy-1-methyl-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine hydrochloride | ||
Canonical SMILES | CCCN[C@]1([H])CCC2=C([C@]1([H])C)C=CC=C2OC.Cl | ||
分子式 | C15H23NO.HCl | 分子量 | 269.81 |
溶解度 | Soluble to 10 mM in Water | 储存条件 | Store at RT |
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。 |
制备储备液 | |||
![]() |
1 mg | 5 mg | 10 mg |
1 mM | 3.7063 mL | 18.5316 mL | 37.0631 mL |
5 mM | 0.7413 mL | 3.7063 mL | 7.4126 mL |
10 mM | 0.3706 mL | 1.8532 mL | 3.7063 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet