Effect of dantrolene sodium on [3H]nitrendipine binding to rat cardiac plasma membranes.

Dantrolene sodium (Dantrium) has antiarrhythmic activity in addition to its direct-acting skeletal muscle relaxant activity. Dantrolene sodium exerts its skeletal muscle relaxant action by reducing Ca2+ release for sarcoplasmic reticulum. The mechanism by which dantrolene sodium produces its antiarrhythmic effects is not well defined. The effects of dantrolene sodium on [3H]nitrendipine binding to rat cardiac plasma membranes were, therefore, investigated to determine whether the antiarrhythmic action involves an interaction with calcium channels. Whereas 1,4-dihydropyridines maximally inhibited [3H]nitrendipine binding with IC50 values less than 1 nM, verapamil and gallopamil (D 600) inhibited the binding not more than 70% with IC50 values at microM concentrations. Dantrolene sodium caused only minimal inhibition at concentrations up to 100 microM. Thus, the antiarrhythmic action of the drug probably involves a mechanism(s) other than an interaction with the nitrendipine binding site of the slow inward calcium channel.

Prediction of human analgesic dosages of nonsteroidal anti-inflammatory drugs (NSAIDs) from analgesic ED50 values in mice.

The oral analgesic activities (ED50's) of 15 NSAIDs were determined in the phenylquinone-induced writhing test in mice. ED50 values (mg/kg) were: acetylsalicylic acid (182), fenclofenac (168), phenylbutazone (129), ibuprofen (82.2), diflunisal (55.6), benoxaprofen (25.4), naproxen (24.1), mefenamic acid (20.7), indomethacin (19.0), meclofenamate sodium (9.60), sulindac (7.20), fenoprofen calcium (3.70), tolmetin (1.30), zomepirac sodium (0.70), and piroxicam (0.44). Significant linear correlations were found between mouse ED50 values and the various recommended human analgesic or anti-inflammatory dosages. Thus, analgesic ED50 values (mg/kg p.o.) in mice (X) may be used to predict human dosages (Y) of NSAIDs according to the equation Y = 8.26X + 535, where Y is the projected human daily dosage (mg).