A 77636 hydrochloride是一种选择性多巴胺D1受体激动剂，其pKi值为7.40±0.09，Ki值为39.8nM，EC50值为1.1nM。
Cas No.:145307-34-2
Sample solution is provided at 25 µL, 10mM.
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A 77636 hydrochloride is a selective dopamine D1 receptor agonist with pKi=7.40±0.09; Ki=39.8nM and EC50=1.1nM. A 77636 is commonly used in Parkinson's disease research [1].
In vitro, pretreatment of SK-N-MC cells with A 77636 (200nM; 1h) led to a persistent elevation of cAMP levels, and can be blocked by SCH 23390 [2]. A 77636 (1-20μM) upregulated the phosphorylation of eIF2α, inhibited proliferation, motility, and bone metastatic activity of 4T1.2 mammary tumor cells and MDA-MB-231 breast cancer cells [3].
In vivo, A 77636 (3μmole/kg; s.c.) increased locomotor activity and decreased the severity of the parkinsonian-like symptoms in marmosets treated with MPTP (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced parkinsonian-like model [1]. A 77636 (3-60mg/kg; s.c.) increased horizontal locomotion and rearing at lower doses in Male hD1 mice [4]. A 77636 (3 and 10mg/kg; i.p.) produced dose-related attenuation and decreased peak responding to cocaine in Swiss-Webster mice [5]. A 77636 (0.1–1.0mg/kg, s.c.) exerted a suppressant effect on food intake in rat, due to a reduction in meal size and duration [6].
References:
[1]. Kebabian, John W., et al. "A 77636: a potent and selective dopamine D1 receptor agonist with antiparkinsonian activity in marmosets." European journal of pharmacology 229.2-3 (1992): 203-209.
[2]. Lin, Chun Wel, et al. "Persistent activation of the dopamine D1 receptor contributes to prolonged receptor desensitization: studies with A 77636." The Journal of pharmacology and experimental therapeutics 276.3 (1996): 1022-1029.
[3]. Minami, Kazumasa, et al. "Inhibitory effects of dopamine receptor D1 agonist on mammary tumor and bone metastasis." Scientific reports 7.1 (2017): 45686.
[4]. Svensson, Kjell A., et al. "An allosteric potentiator of the dopamine D1 receptor increases locomotor activity in human D1 knock-in mice without causing stereotypy or tachyphylaxis." The Journal of pharmacology and experimental therapeutics 360.1 (2017): 117-128.
[5]. Chausmer, Allison L., and Jonathan L. Katz. "Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A 77636, with cocaine: locomotor activity and drug discrimination studies in rodents." Psychopharmacology 159.2 (2002): 145-153.
A 77636 hydrochloride是一种选择性多巴胺D1受体激动剂，其pKi值为7.40±0.09，Ki值为39.8nM，EC50值为1.1nM。A 77636常用于帕金森病相关研究[1]。
体外实验中，A 77636（200nM；1h）预处理SK-N-MC细胞可持续升高细胞内cAMP水平，该作用可被SCH 23390阻断[2]。A 77636（1-20μM）可上调eIF2α的磷酸化水平，并抑制4T1.2乳腺肿瘤细胞及MDA-MB-231乳腺癌细胞的增殖、迁移以及骨转移活性[3]。
体内实验中，A 77636（3μmol/kg；皮下注射）可增加MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）诱导的帕金森样狨猴模型的运动活动，并减轻帕金森样症状的严重程度[1]。A 77636（3-60mg/kg；皮下注射）可增加雄性hD1小鼠的水平活动和竖立行为，且在低剂量时作用更明显[4]。A 77636（3，10mg/kg；腹腔注射）可剂量依赖性减弱可卡因诱导的行为反应，并降低Swiss-Webster小鼠对可卡因的峰值反应[5]。A 77636（0.1-1.0mg/kg；皮下注射）可通过减少进食量和进食持续时间，对大鼠食物摄入产生抑制作用[6]。
| Cell experiment [1]: | |
Cell lines | MDA-MB-231 cells |
Preparation Method | 4T1.2 mouse mammary tumor cells were cultured in DMEM, the culture media contained 10% fetal bovine serum (FBS) and antibiotics (50units/ml penicillin, and 50μg/ml streptomycin). Cells were maintained at 37°C and 5% CO2 in a humidified incubator. Then add 2, 5, and 10μM A 77636 in the culture media for 32-48h. |
Reaction Conditions | 2, 5, and 10μM; 32-48h |
Applications | A 77636 (2, 5, and 10 μM) reduced the cellular motility of MDA-MB-231 cells in a dose-dependent manner in the wound healing scratch assay. |
| Animal experiment [2]: | |
Animal models | Male hD1 mice, 8–10 weeks old |
Preparation Method | Mice were placed inside individual locomotor activity (LMA) boxes for 1 hour during an acclimation period. Mice were then dosed with test compounds (oral or subcutaneous) and were replaced inside individual LMA boxes for the start of LMA. Photocell activity (total ambulations) was collected for 60 minutes using software from Hamilton Kinder. DETQ was dissolved in 20% 2-hydroxypropyl-β-cyclodextrin, and D1 agonists SKF 82958 and A 77636 and D1 antagonist SCH39166 were dissolved in 0.9% dihydrexidine saline. |
Dosage form | 3-60mg/kg; s.c. |
Applications | The D1 agonists SKF 82958 and A 77636 showed an increase in horizontal locomotion and rearing at lower doses. |
References: | |
| Cas No. | 145307-34-2 | SDF | |
| 化学名 | (1R,3S)-3-((1s,3R,5R,7S)-adamantan-1-yl)-1-(aminomethyl)isochroman-5,6-diol hydrochloride | ||
| Canonical SMILES | OC(C1=C(C=C2)[C@H](CN)O[C@@H](C1)[C@]3(C[C@H](C4)C5)C[C@@H]4C[C@H]5C3)=C2O.Cl | ||
| 分子式 | C20H27NO3.HCl | 分子量 | 365.9 |
| 溶解度 | DMF: 33 mg/ml,DMSO: 33 mg/ml,Ethanol: 33 mg/ml,Ethanol:PBS (pH 7.2) (1:6): 0.14 mg/ml | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.733 mL | 13.6649 mL | 27.3299 mL |
| 5 mM | 546.6 μL | 2.733 mL | 5.466 mL |
| 10 mM | 273.3 μL | 1.3665 mL | 2.733 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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2.
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- Purity: >99.50% Appearance: A solid
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