Misík V, Stasko A, Gergeĺ D, Ondrias K
Institute of Experimental Pharmacology, Centre of Physiological Sciences, Slovak Academy of Sciences, Bratislava, Czechoslovakia.
Mol Pharmacol. 1991 Sep;40(3):435-9.
Nifedipine [1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic+ ++ acid dimethyl ester] and nimodipine [1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic+ ++ acid 2-methoxyethyl 1-methylethyl ester], incorporated into diheptanoylphosphatidylcholine liposomes, which were used as a drug carrier system, slightly inhibited lipid peroxidation (induced by tert-butylhydroperoxide and Fe2+) in rat heart homogenate. Illumination of nimodipine had no effect on its antioxidant potency, whereas illuminated nifedipine was several times more effective than nonilluminated drug. On illumination, nifedipine converts to 2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester (NTP). NTP formed stable radicals when interacting with the rat heart homogenate and dioleoylphosphatidylcholine, as detected by EPR spectroscopy. No radical formation was observed if nonilluminated nifedipine and nimodipine or illuminated nimodipine were used. The spin density of the unpaired electron in the NTP-adduct was centered on the nitrogen derived from its nitroso group. The motion of the NTP-adduct radical was restricted, indicating that the radicals were located in the membrane of the homogenate and not in the buffer system. Only NTP (not nifedipine or nimodipine) was effective in trapping free radicals formed by the thermal or photoinduced decomposition of 2,2'-azobisisobutyronitrile and radicals formed by photolysis of di-tert-butylperoxide. The antioxidant and spin-trapping properties of NTP in our systems were attributed to its nitroso group.
硝苯地平[1,4 - 二氢 - 2,6 - 二甲基 - 4 - (2 - 硝基苯基)-3,5 - 吡啶二甲酸二甲酯]和尼莫地平[1,4 - 二氢 - 2,6 - 二甲基 - 4 - (3 - 硝基苯基)-3,5 - 吡啶二甲酸2 - 甲氧基乙基1 - 甲基乙酯]被包裹于二庚酰磷脂酰胆碱脂质体中作为药物载体系统，它们对大鼠心脏匀浆中的脂质过氧化（由叔丁基过氧化氢和Fe2 +诱导）有轻微抑制作用。光照尼莫地平对其抗氧化能力无影响，而光照后的硝苯地平比未光照的药物有效几倍。光照时，硝苯地平转化为2,6 - 二甲基 - 4 - (2 - 亚硝基苯基)-3,5 - 吡啶二甲酸二甲酯（NTP）。通过电子顺磁共振光谱检测发现，NTP与大鼠心脏匀浆和二油酰磷脂酰胆碱相互作用时会形成稳定的自由基。若使用未光照的硝苯地平和尼莫地平或光照后的尼莫地平，则未观察到自由基形成。NTP加合物中未成对电子的自旋密度集中在源自其亚硝基的氮原子上。NTP加合物自由基的运动受到限制，这表明自由基位于匀浆的膜中而非缓冲系统中。只有NTP（而非硝苯地平或尼莫地平）能有效捕获由2,2'-偶氮二异丁腈热分解或光分解产生的自由基以及二叔丁基过氧化物光解产生的自由基。在我们的系统中，NTP的抗氧化和自旋捕获特性归因于其亚硝基。
