Westerveld G J, Scheeren R A, Dekker I, Griffioen D H, Voss H P, Bast A
Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit, Netherlands.
Eur J Pharmacol. 1995 Sep 15;291(1):27-31. doi: 10.1016/0922-4106(95)90185-x.
Anti-oxidant actions of oxymethazoline and xylomethazoline were investigated by measuring inhibition of microsomal lipid peroxidation and hydroxyl radical scavenging activity. Oxymethazoline was shown to be a potent inhibitor of lipid peroxidation (IC50 = 4.9 microM at t = 15 min, IC50 = 8.1 microM at t = 30 min), in contrast to xylomethazoline. Both compounds were excellent hydroxyl radical scavengers. Their rate constants (ks = 1.1 x 10(12) M-1 s-1 for oxymethazoline and ks = 4.7 x 10(10) M-1 s-1 for xylomethazoline) exceeded the rate constant of a known powerful scavenger cimetidine (ks = 1.8 x 10(10) M-1 s-1). The difference in inhibiting lipid peroxidation might be explained by the fact that only oxymethazoline has a hydroxy group which can donate a hydrogen atom and terminate the chain reaction of lipid peroxidation. The mechanism of hydroxyl radical scavenging activity is still unclear. Moreover oxymethazoline seems to have a different mode of action in scavenging hydroxyl radicals than xylomethazoline and cimetidine which results in an extremely high rate constant. Because oxidants play a role in tissue damage in inflammation, it was hypothesized that especially oxymethazoline and to a lesser extent xylomethazoline may have an additional beneficial effect, due to their anti-oxidant properties, in the topical treatment of nasal inflammation.
通过测量对微粒体脂质过氧化的抑制作用和羟自由基清除活性，研究了氧甲唑啉和赛洛唑啉的抗氧化作用。与赛洛唑啉相比，氧甲唑啉被证明是一种有效的脂质过氧化抑制剂（在t = 15分钟时IC50 = 4.9 microM，在t = 30分钟时IC50 = 8.1 microM）。两种化合物都是出色的羟自由基清除剂。它们的速率常数（氧甲唑啉的ks = 1.1 x 10(12) M-1 s-1，赛洛唑啉的ks = 4.7 x 10(10) M-1 s-1）超过了已知强效清除剂西咪替丁的速率常数（ks = 1.8 x 10(10) M-1 s-1）。抑制脂质过氧化的差异可能是由于只有氧甲唑啉有一个可以提供氢原子并终止脂质过氧化链反应的羟基这一事实。羟自由基清除活性的机制仍不清楚。此外，氧甲唑啉在清除羟自由基方面似乎具有与赛洛唑啉和西咪替丁不同的作用模式，这导致了极高的速率常数。由于氧化剂在炎症中的组织损伤中起作用，因此推测特别是氧甲唑啉，在较小程度上还有赛洛唑啉，可能因其抗氧化特性在鼻炎症的局部治疗中具有额外的有益作用。
