Dantrolene sodium (1) is a direct skeletal muscle relaxant, effective in the treatment of malignant hyperthermia. However, no study on the intrinsic hypothermic activity of this drug has yet been reported. This paper describes the reduction in core body temperature of mice by dantrolene sodium and its corresponding analogues, 1‐[[[[5‐(4‐nitrobenzene) thio]‐2‐furanyl]‐methylene]‐amino]‐2, 4‐imidazolidinedione (2) and 1‐[[[[5‐(4‐nitrobenzene)ethenyl]‐2‐furanyl]‐methylene]‐amino]‐2,4‐imidazolidin‐edione (3). Compounds 2 and 3 have been shown to have higher and comparable muscle relaxant activity, respectively, compared with 1.
All compounds reduced core body temperature in mice at a dose of 40 mg kg−1. Compared with 1, compound 2 exhibited similar activity but compound 3 was less active.
Molecular modelling studies indicate that the semi‐folded conformers of these compounds are responsible for their biological activity and the lower activity of 3 might be due to the restraint in conformational freedom imposed by the presence of the —C = C— bond which results in some stable folded conformers.
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