临床前的PF9404C,一氧化氮供体与β受体阻断属性。
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Villarroya M,洛佩兹毫克,de Pascual R,加西亚AG)
临床前的PF9404C,一氧化氮供体与β受体阻断属性。
Cardiovasc毒品启2005年夏季;23 (2):149 - 60。
- PubMed ID
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16007231 (在PubMed]
- 文摘
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PF9404C ((2), (2) 3-isopropylamine, 1 - [4 - (2, 3-dinitroxy) propoxymethyl] -phenoxy-2 -propranol)是s diesteroisomer小说的该项受体阻滞剂vasorelaxing属性。它会导致浓度放松的大鼠主动脉螺旋带预约10(6)米去甲肾上腺素(NE);IC50 33海里)。是均等的硝酸甘油(NTG);IC50 49海里),但更强大的比硝酸异山梨酯(ISD;IC50 15000海里)。在大鼠主动脉平滑肌细胞,在10 microM PF9404C增加cGMP的形成从基底条件3 pmol /毫克蛋白53 pmol /毫克蛋白,表明vasorelaxing效应的机制涉及到代没有放缓。这是支持的事实(i) ODQ(拦截器的鸟苷酸环化酶)抑制PF9404C血管扩张性效果;和(2)PF9404C无法产生间接衡量格里斯反应。电动豚鼠左心房,PF9404C街区的变力影响异丙肾上腺素浓度的方式。 Its IC50 (30 nM) was similar to that of S-propranolol (22.4 nM) and lower than that of metoprolol (120 nM) or atenolol (192 nM). The beta adrenergic ligand (-)-[3H]-CGP12177 (4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2- one hydrochloride) (0.2 nM) is displaced from its binding sites in rat brain membranes with a K(i) of 7, 17, 170, and 1200 nM for PF9404C, S-(-)propranolol, metoprolol, and atenolol, respectively. PF9404C blocks 45Ca2+ entry into bovine adrenal chromaffin cells induced by direct depolarization with 70 mM K+ or by the nicotinic agonist dimethylphenylpiperazinium (DMPP). PF9404C exhibits about 3-fold higher potency than NTG to relax the majority of the vessels studied, especially when they were contracted with K+, and shows a certain selectivity of action for the renal artery. It produces auto-tolerance that is ca. 20-fold less pronounced than that observed with NTG. Cross-tolerance in preparations pre-exposed to PF9404C and later relaxed with NTG, was much greater than auto-tolerance. This makes PF9404C a useful pharmacological tool for the development of novel NO-donor compounds with a lesser degree of vascular tolerance than those currently available.