COMPARISON OF SKELETAL, CARDIAC, AND SMOOTH-MUSCLE ACTIONS OF DANTROLENE SODIUM - SKELETAL-MUSCLE RELAXANT

Abstract

Dantrolene sodium, a skeletal muscle relaxant, was proposed to inhibit the release of Ca2+ from the sarcoplasmic reticulum. Such a mechanism suggested that other muscle contractile systems operating with the same Ca2+ denominator should also be affected by the drug. Dantrolene sodium effects on smooth, cardiac and skeletal muscle were evaluated with in situ and in vitro techniques. In anesthetized dogs, in situ skeletal muscle contractions were inhibited in a dose-dependent manner, but cardiac muscle contractions were not. Effects on intestinal smooth muscle responses were highly variable and of short duration. In vitro, ED50 values were developed with dantrolene sodium (0.15-120 mg/l) in DMSO [dimethylsulfoxide] for each tissue. Skeletal muscle was the most sensitive (ED50 = 4.1 mg/l), while cardiac muscle contractions were not inhibited by the drug, and intestinal smooth muscle (ED50 = 59.0 mg/l) was approximately 1/14 as sensitive as skeletal muscle. Skeletal muscle was uniquely sensitive to dantrolene sodium. A hypothesis for this specific action was offered.