Diltiazem, a benzothiazepine calcium channel blocker used widely in cardiovascular therapy, protected mice against death by ionizing radiation. Diltiazem was active in male and female C3H mice and could be administered subcutaneously or intraperitoneally. Protection was also seen in BALB/c, C57B1/6, and NMRI mice. Moderate activity was afforded by oral administration of effective levels of diltiazem. Injection at 10 or 30 min before irradiation was similarly effective, but injection 2 h prior to the irradiation provided only marginal protection. The dihydropyridine calcium channel blockers nifedipine and nimodipine were also effective, but since these compounds were in an ethanol-containing solvent their radioprotective activity had to be distinguished from that of the ethanol. Synergistic effects occurred by combining diltiazem with zinc aspartate, dimethyl sulfoxide, and nifedipine. Protection by calcium antagonists may be due to interference with the damaging cellular influx of calcium after membrane injury by radiation-induced free radicals or by their direct inactivation. Calcium antagonists could play a role as less toxic radioprotectors, providing modest dose reduction factors but without the prohibitive side effects of aminothiols such as WR-2721.
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Research Article| January 01 1993
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G. L. Floersheim; Radioprotective Effects of Calcium Antagonists Used Alone or with Other Types of Radioprotectors. Radiat Res 1 January 1993; 133 (1): 80–87. doi: https://doi.org/10.2307/3578260
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