Profile of the oppositely acting enantiomers of the dihydropyridine 202-791 in cardiac preparations: receptor binding, electrophysiological, and pharmacological studies.
Receptor binding, electrophysiological, and inotropic effects of the pure dihydropyridine enantiomers (+)S202-791 and (-)R202-791 were studied in cardiac preparations. The KI for (+)S202-791 binding correlated with the ED50's for an increase in contractile force and an increase in calcium current, the latter effect occurring at depolarized as well as resting holding potentials. The KI for (-)R202-791 binding was much lower than the IC50's for inhibition of calcium current measured at holding potentials of -80 or -90 mV and a negative inotropic effect, but correlated closely with the IC50 for inhibition of calcium current measured at -30 mV. Thus, (+)S202-791, is a voltage independent calcium channel activator and (-)R202-791 is a voltage dependent calcium channel inhibitor.
J S
JS
Williams
I L
IL
Grupp
G
G
Grupp
P L
PL
Vaghy
L
L
Dumont
A
A
Schwartz
A
A
Yatani
S
S
Hamilton
A M
AM
Brown
D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D004095:Dihydropyridines; D004285:Dogs; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism; D009568:Nitrendipine; D010210:Papillary Muscles / Q000502:physiology; D011725:Pyridines / Q000378:metabolism* / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D016276:Ventricular Function
D004095:Dihydropyridines; D007473:Ion Channels; D011725:Pyridines; C038806:1,4-dihydropyridine; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium