Effect of dantrolene sodium on the contractility of rabbit jejunum in vitro

Abstract

The effect of dantrolene sodium on the spontaneous contractions of rabbit jejunum was studied in vitro. Dantrolene sodium (4.5 × 10 −6 to 4.5 × 10 −4 M) reversibly decreased the amplitude of contractions in a dose-dependent manner. ED 50 was found to be about 7.9 × 10 −5 M. Its effect was biphasic in that a period of potentiation preceded that of suppression of contractions. Lowering or increasing (2.5 fold in each direction) the calcium concentration of bathing media did not affect the suppression of contraction caused by dantrolene sodium to any significant degree. Caffeine but not quinne was found to be able to restore the activity of the intestine to normal after a 50% inhibition caused by dantrolene sodium. Dantrolene sodium, verapamil and nifedipine were able to shift the dose-response curves of calcium in potassium-depolarized rabbit jejunum to the right and pA 2 values were found to be 4.18, 7.76 and 8.47 respectively. These data indicate that the effect of dantrolene on smooth muscle is mediated via inhibition of calcium movement across the membrane.