The effect of EU4093 (azumolene sodium) on the contraction of intrafusal muscle in the soleus muscle of the anaesthetized rat

1. EU4093 (azumolene sodium) is a direct acting, skeletal muscle relaxant with structural similarities to dantrolene sodium in that the para-nitro phenyl group of dantrolene sodium is replaced by a para-bromo phenyl group. 2. The effect of EU4093 on the twitch of the intact rat soleus preparation is nearly maximal at a dose of 20 mg kg-1. This dose of EU4093 reduces the amplitude of the twitch to 31.9% of the control value. By comparison, dantrolene sodium reduced the twitch amplitude to 31.3% of the control value at a dose of 5 mg kg-1. 3. The contraction of intrafusal muscle as measured by the response of spindle afferent discharge was also reduced by EU4093. 4. The most significant difference between the effect of EU4093 and dantrolene sodium on the contraction of intrafusal muscle was that EU4093 had an appreciable depressant action at high stimulation frequencies at which dantrolene sodium had only a minimal relaxant effect on the intrafusal muscle contraction. 5. The significance of this difference in the actions of EU4093 and dantrolene sodium is discussed in terms of the possible effect of the drug in the intact animal and human patient. It is concluded that, because the discharge frequency is not likely to move into the high frequency range at which dantrolene sodium and EU4093 have significantly different effects, the overall effect of these two drugs is likely to be similar.