The pharmacology of hydrated 1 less than ([5-(3,4-dichlorophenyl)-2-furanyl]methylene) amino greater than-2,4,-imidazolidinedione
sodium salt (
clodanolene sodium), as skeletal-muscle contraction antagonist, is presented.
Clodanolene sodium is remarkable in that it has no measurable direct effect on the peripheral or central nervous systmes. Skeletal muscle relaxation can be achieved with this
drug at doses that do not affect motor coordination. Rats receiving
clodanolene sodium for up to 30 days evidenced a downward trend in gross observation score of skeletal muscle relaxation, but the extent of twitch inhibition was the same on day 30 as on day 1. In an animal model of
muscle spasticity (Straub-tail mouse),
clodanolene sodium has been shown to be more efficacious for induction of skeletal muscle relaxation than
neuromuscular blocking agents,
local anesthetics, or
centrally-acting muscle relaxants.
Clodanolene sodium's mode of action has been identified as specific for skeletal muscle. It has no measurable effect on neuromuscular transmission or on the electrically excitable surface membrane. Indirect evidence indicates that the site of action of
clodanolene sodium, like that of
dantrolene sodium, is within the muscle cell and is related to
caffeine-sensitive
calcium stores. Its skeletal-muscle relaxant activity, we suggest results from a decrease in the release of
calcium from the sarcoplasmic reticulum.