A COMPARISON OF THE POTENCY AND SPECIFICITY OF THE DIRECT MUSCLE-RELAXANT ACTIVITY OF AZUMOLENE AND DANTROLENE

Dantrolene is a unique directly acting skeletal muscle relaxant that is clinically useful in the treatment of chronic muscle spasticity and malignant hyperthermia. Azumolene is a new dantrolene-like drug that has better aqueous solubility and that may also be of use in the treatment of acute muscle spasm. Potency of both compounds was determined in the anesthetized, curarized rat gastrocnemius (using different routes of administration) and the isolated chick biventer muscle preparations. The specificity of effects in vitro was evaluated by comparing effects in the chick biventer with those seen in the rat aortic strip. Route of administration governed potency for both drugs, with rank order i.v., i.p., and i.d. being the least potent. In vivo, dantrolene was approximately twice as potent as azumolene when administered by any of the routes tested. However, both drugs are equipotent in vitro. Reasons for the discrepancy between in vivo and in vitro potencies are discussed. The muscle relaxant effects of both azumolene and dantrolene are specific for skeletal muscle, being 10-fold more potent in skeletal than in arterial smooth muscle. The reasons for this specificity are probably due to basic differences in the physiology of smooth and skeletal muscle. We conclude that the new agent, azumolene, is a specific, potent skeletal muscle relaxant with properties qualitatively similar to those of dantrolene.