Muscle relaxant action of dantrolene sodium in rats.
The relationship between the muscle relaxant action and intramuscular concentration of unchanged dantrolene sodium [1-[5-(p-natrophenyl) furfurylidene amino] hydantoin sodium hemiheptahydrate, dantrolene] by intravenous administration of dantrolene was examined in rats. The mechanism of the muscle relaxant action of dantrolene was also examined. Dantrolene, unlike tolperisone, a centrally acting muscle relaxant, dose-dependently inhibited twitch contraction evoked by electrical stimulation of both the muscle and the phrenic nerve in the rat isolated phrenic nerve-diaphragm preparation to a similar extent (IC50: 9.5 and 6.5 x 10(-6) M, respectively). Inhibition of both twitch contractions by dantrolene (50 microM) was antagonized by 4-aminopyridine (42.5 microM) and caffeine (4 mM). The twitch contraction of the gastrocnemius muscle elicited by sciatic nerve stimulation was inhibited by intravenous administration of dantrolene in a dose-dependent manner. The effective intramuscular concentration of dantrolene producing 50% depression (ID50) was 3.4 micrograms/g tissue, equal to about 1 x 10(-5) M. We thus found a close relationship between IC50 in vitro and ID50 in situ. Furthermore, this study raised the possibility that dantrolene produces its muscle relaxant action by affecting peripheral muscular Ca2+ mobilization.
Saito
S
S
Yamanouchi Pharmaceutical Co. Ltd., Clinical Pharmacology Research Laboratories, Tokyo, Japan.
Harada
M
M
Yamamoto
M
M
Takagi
H
H
Saito
K
K
Konno
Y
Y
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D003620:Dantrolene / Q000378:metabolism*; D004347:Drug Interactions; D004558:Electric Stimulation; D007275:Injections, Intravenous; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D010791:Phrenic Nerve / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission
D002110:Caffeine; D015761:4-Aminopyridine; D003620:Dantrolene