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]。