Effects of dantrolene sodium on respiratory and other muscles and on respiratory parameters in the anaesthetised cat

The effects of intravenous dantrolene sodium on contractions of the tibialis anterior, the flexor digitorum longus, the soleus and the diaphragm muscles, and on respiratory parameters, blood pressure and heart rate were recorded in cats under chloralose anaesthesia. Dantrolene maximally depressed twitches of the tibialis anterior and flexor digitorum loncles to a significantly greater extent (ca. 90%) than it depressed those of the soleus and diaphragm muscles (ca. 72%). When the muscles were indirectly stimulated at frequencies high enough to produce complete fusion of responses, the depressant action of dantrolene was largely masked. The onset of this “break through” effect was evident with paired stimuli, and was maximal with trains of about 6 stimuli. Dantrolene was without effect on blood pressure and heart rate in all experiments; the slight effects that accompanied each injection were entirely attributable to the solvent (propylene glycol). In 8 out of 12 experiments, dantrolene was without any detectable effect on breathing. In one cat, however, which happened to be unusually deeply anaesthetised, dantrolene produced a decrease in the frequency of breathing and the animal tended to hold each breath for longer than usual. In 3 out of the 12 cats, dantrolene produced a slight increase in transpulmonary pressure, a slight reduction in tidal volume and a slight shortening of the duration of each respiratory cycle with no alteration in the frequency of breathing. It is proposed that the lack of effect of dantrolene on the respiratory parameters in most experiments was the result of a reflex increase in the frequency of discharge from the respiratory centre to the extent that resistant tetanic contractions of the respiratory muscles were evoked.