Spin-trapping and antioxidant properties of illuminated and nonilluminated nifedipine and nimodipine in heart homogenate and model system.

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.