Effect of dantrolene sodium on [3H]nitrendipine binding to rat cardiac plasma membranes.
Dantrolene sodium (Dantrium) has antiarrhythmic activity in addition to its direct-acting skeletal muscle relaxant activity. Dantrolene sodium exerts its skeletal muscle relaxant action by reducing Ca2+ release for sarcoplasmic reticulum. The mechanism by which dantrolene sodium produces its antiarrhythmic effects is not well defined. The effects of dantrolene sodium on [3H]nitrendipine binding to rat cardiac plasma membranes were, therefore, investigated to determine whether the antiarrhythmic action involves an interaction with calcium channels. Whereas 1,4-dihydropyridines maximally inhibited [3H]nitrendipine binding with IC50 values less than 1 nM, verapamil and gallopamil (D 600) inhibited the binding not more than 70% with IC50 values at microM concentrations. Dantrolene sodium caused only minimal inhibition at concentrations up to 100 microM. Thus, the antiarrhythmic action of the drug probably involves a mechanism(s) other than an interaction with the nitrendipine binding site of the slow inward calcium channel.
Pong
S F
SF
Demuth
S M
SM
White
R L
RL
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism; D009568:Nitrendipine; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D009568:Nitrendipine; D003620:Dantrolene; D009543:Nifedipine