Reversal of Dantrolene Sodium-induced Depression of Skeletal Muscle in the Cat

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Abstract
Dantrolene sodium, a muscle relaxant, does not habe a clinically useful antagonist. The study was undertaken to test the efficacies of germine monoacetate, 4-aminopyridine, neostigmine and CaCl2 as possible agents for the reversal of the direct skeletal muscle depression produced by dantrolene sodium in the cat anesthetized with .alpha.-chloralose. Depression of the indirectly elicited twitch responses (0.1 Hz) of the tibialis anterior muscle by 25, 50, 75 and 84% was produced by dantrolene, 0.16, 0.36, 0.88 and 1.13% mg/kg, respectively; spontaneous recovery of twitch tension during the subsequent 30 min was negligible. After the 30 min observation period had elapsed, one of the reversal agents under study was given (i.v.) in divided doses at intervals of 10 min (5 cats for each agent). Germine monoacetate (2 .times. 0.5 mg/kg) immediately reversed the dantrolene-induced twitch depression, with an overshoot that persisted for an hour. 4-Aminopyridine (4 .times. 0.5 mg/kg) caused a steady but incomplete reversal to 17% depression, 30 min after the last dose. Neostigmine (4 .times. 0.04 mg/kg) caused an immediate, but transient, reversal of the twitch depression, with overshoot. CaCl2 (4 .times. 10 mg/kg) was without effect. Germine monoacetate is the drug of choice for reversal of the muscle depression produced by dantrolene sodium in the cat.