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In vivo EPR evidence for free radical adducts of nifedipine
Author(s) -
Fujii Hirotada,
Berliner Lawrence J.
Publication year - 1999
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/(sici)1522-2594(199910)42:4<691::aid-mrm10>3.0.co;2-5
Subject(s) - chemistry , in vivo , nifedipine , electron paramagnetic resonance , radical , ex vivo , photochemistry , biochemistry , calcium , nuclear magnetic resonance , in vitro , organic chemistry , biology , physics , microbiology and biotechnology
Nifedipine [3,5‐pyridinedicarboxylic acid, 1,4‐dihydro‐2,6‐dimethyl‐4‐(2‐nitrophenyl)‐dimethyl ester] is a calcium channel blocker that has been widely used as a prescription drug for patients with hypertension. After illumination by ordinary light for 24 hr, nifedipine is converted completely to its nitroso analog without further photochemical degradation. Evidence for stable, nitroxyl‐like free radical generation in mice was observed 15 min after intramuscular (i.m.) or intraperitoneal (i.p.) injection of illuminated nifedipine as monitored by in vivo L‐band electron paramagnetic resonance (EPR) spectrometry. This was confirmed in more detail by ex vivo measurements on excised muscle and liver tissue. The nature of these radicals was surmised by comparing the reaction of illuminated nitroso‐nifedipine with polyunsaturated fatty acids. Surprisingly, identical radical spectra were detected from excised liver doped with nonilluminated nifedipine, suggesting that this drug can be enzymatically converted in vivo to its nitroso analog without the requirement for illumination. This is one of the first reports of in vivo EPR evidence for a class of unsaturated fatty acid radical conjugates resulting from the normal metabolism of a common drug. Magn Reson Med 42:691–694, 1999. © 1999 Wiley‐Liss, Inc.