Prazosin HCl is a specific antagonist of the α1-adrenergic receptor (α1-AR), with binding constants (Ki values) of 0.2, 0.25, and 0.32nM for human recombinant α1A-AR, α1B-AR, and α1D-AR, respectively, and 340 and 3.7nM for α2-AR (in HT-29 cells expressing α2A-AR and NG108 cells expressing α2B-AR) [1-2]. The α1-AR belongs to the seven-transmembrane structure and G protein-coupled receptor superfamily, and α1-AR located in the central and peripheral nervous systems have significant therapeutic significance [3]. Prazosin HCl can have anti-inflammatory effects, relieve anxiety, alleviate panic, prevent memory decline, and regulate the analgesic effect of opioid drugs, and can be used in the research of hypertension and Alzheimer's disease [4].
In vitro, Prazosin HCl (0, 2.5, 5, 7.5, 10, 15, 20, 30, 40, and 50μM; 24h) dose-dependently reduced the viability of MG63 and 143B cells and significantly weakened the cell migration and invasion ability. Prazosin HCl inhibits the Akt/mTOR pathway by down-regulating the phosphorylation levels of Akt and mTOR and the expression of P70 and cyclin D1 [5]. Prazosin HCl (30μM; 1h) pretreatment significantly increased the cytotoxicity of docetaxel-induced PC-3 and -LNCaP cells [6].
In vivo, Prazosin HCl (1mg/kg/day; 2 weeks; i.p.) treatment can prevent memory decline in Alzheimer's disease (AD) mice, increase the anti-inflammatory response and astrocyte activation of mice, and significantly increase the number of GFAP-positive cells and neuronal cells [1]. Prazosin HCl (0.01, 0.1, 0.25, 0.5, 1, and 2mg/kg/day; single-dose; i.p.) enhances the analgesic effect of morphine in mice in the tail flick test, while Prazosin HCl alone has no analgesic effect [7].
References:
[1] Katsouri L, Vizcaychipi MP, McArthur S, et al. Prazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease. Neurobiol Aging. 2013;34(4):1105-1115.
[2] Bylund DB, Ray-Prenger C. Alpha-2A and alpha-2B adrenergic receptor subtypes: attenuation of cyclic AMP production in cell lines containing only one receptor subtype. J Pharmacol Exp Ther. 1989;251(2):640-644.
[3] Sarma P K S, Tiwari A, Pal A. α1-Adrenoceptors as potential therapeutic targets[J]. Expert Opinion on Therapeutic Patents, 2005, 15(10): 1333-1351.
[4] Ozdoğan UK, Lähdesmäki J, Scheinin M. Influence of prazosin and clonidine on morphine analgesia, tolerance and withdrawal in mice. Eur J Pharmacol. 2003;460(2-3):127-134.
[5] An M, Ma W H, Jia H W, et al. Prazosin inhibits the growth and mobility of osteosarcoma cells[J]. Translational cancer research, 2019, 8(5): 1997.
[6] Spencer B H, McDermott C M, Chess-Williams R, et al. Prazosin but not tamsulosin sensitises PC-3 and LNCaP prostate cancer cells to docetaxel[J]. Pharmacology, 2018, 102(1-2): 17-25.
[7] Ozdoğan UK, Lähdesmäki J, Scheinin M. Influence of prazosin and clonidine on morphine analgesia, tolerance and withdrawal in mice. Eur J Pharmacol. 2003;460(2-3):127-134.
Prazosin HCl是一种特异性的α1-肾上腺素能受体（α1-AR）的拮抗剂，与人类重组α1A-AR、α1B-AR和α1D-AR的结合常数（Ki值）分别为0.2、0.25和0.32nM，与α2-AR的Ki值分别为340和3.7nM（在表达α2A-AR 的 HT-29 细胞和表达α2B-AR 的 NG108 细胞中） [1-2]。α1-AR属于七跨膜结构、与G蛋白偶联的受体超家族，位于中枢和外周神经系统中的α1-AR具有重要的治疗意义 [3]。Prazosin HCl可以抗炎、缓解焦虑、缓解恐慌，防止记忆衰退，调节阿片类药物的镇痛作用，可用于高血压和阿尔兹海默症研究 [4]。
在体外，Prazosin HCl（0, 2.5, 5, 7.5, 10, 15, 20, 30, 40, and 50μM; 24h）剂量依赖性地降低了MG63和143B细胞的活力，并显著减弱了细胞迁移和侵袭能力。Prazosin HCl通过下调Akt和mTOR磷酸化水平以及P70和细胞周期蛋白D1的表达来抑制Akt/mTOR通路 [5]。Prazosin HCl（30μM; 1h）预处理显著增加了多西紫杉醇诱导的PC-3和-LNCaP细胞的细胞毒性 [6]。
在体内，Prazosin HCl（1mg/kg/day; 两周; i.p.）治疗可预防阿兹海默病（AD）小鼠的记忆衰退，增加了小鼠的抗炎反应和星形胶质细胞活化，并显著增加了GFAP阳性细胞和神经元细胞数量 [1]。Prazosin HCl（0.01, 0.1, 0.25, 0.5, 1 and 2mg/kg/day; single-dose; i.p.）增强了吗啡对尾部拍击实验中小鼠的镇痛作用，而Prazosin HCl单独给药无镇痛作用 [7]。