Ergün H, Ayhan I H, Tulunay F C
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Ankara University, Sihhiye, Turkey.
Gen Pharmacol. 1999 Sep;33(3):237-41. doi: 10.1016/s0306-3623(99)00013-0.
Metamizol produced a dose- and time-dependent relaxation in rabbit thoracic aorta smooth muscle that was precontracted by phenylephrine. Such a relaxation was not observed with indomethacin, which is also a nonsteroidal anti-inflammatory drug. The relaxing effect of metamizol was independent of the presence of vascular endothelium. Tetraethylammonium (a calcium-activated potassium channel inhibitor), glybenclamide (an ATP-dependent potassium channel inhibitor), indomethacin (a cyclooxygenase inhibitor), and methylene blue (a soluble guanylate cyclase inhibitor) did not have any effect on metamizol-induced relaxation response. Metamizol did not produce any relaxation effect on aortic smooth muscle when KCl (30, 60, and 117 mM KCl) was used instead of phenylephrine to precontract the preparation. Ouabain (a Na-K ATPase pump inhibitor) showed a dose-dependent inhibition on metamizol's relaxation response. However, in potassium-free medium, which is an alternative way to block the Na-K ATPase pump, no inhibition in metamizol-induced relaxation response was observed. When metamizol was incubated for 2 h in organ-bath conditions before evaluating its relaxing effect, it produced a relatively faster relaxation, indicating that the relaxing effect of metamizol is produced by one of its (active) spontaneous degradation products (possibly 4-methylaminoantipyrine).
安乃近对由去氧肾上腺素预收缩的兔胸主动脉平滑肌产生剂量和时间依赖性舒张作用。同样作为非甾体抗炎药的吲哚美辛未观察到这种舒张作用。安乃近的舒张作用与血管内皮的存在无关。四乙铵（一种钙激活钾通道抑制剂）、格列本脲（一种ATP依赖性钾通道抑制剂）、吲哚美辛（一种环氧化酶抑制剂）和亚甲蓝（一种可溶性鸟苷酸环化酶抑制剂）对安乃近诱导的舒张反应均无任何影响。当使用氯化钾（30、60和117 mM氯化钾）代替去氧肾上腺素预收缩标本时，安乃近对主动脉平滑肌未产生任何舒张作用。哇巴因（一种钠钾ATP酶泵抑制剂）对安乃近的舒张反应呈剂量依赖性抑制。然而，在无钾培养基中（这是阻断钠钾ATP酶泵的另一种方法），未观察到对安乃近诱导的舒张反应的抑制作用。在评估其舒张作用前，将安乃近在器官浴条件下孵育2小时，它产生了相对较快的舒张，表明安乃近的舒张作用是由其一种（活性）自发降解产物（可能是4-甲基氨基安替比林）产生的。
