F90927: a new member in the class of cardioactive steroids.
F90927 is a newly developed cardioactive drug with a steroid-like structure. It acts directly and agonistically on the cardiac L-type Ca2+ channel by shifting its voltage-dependent activation toward more negative potentials. This leads to an increased influx of Ca2+ and, therefore, to a stronger contraction; however, no arrhythmias occur. Calcium current stimulation can already be observed at nanomolar concentrations, but higher concentrations of F90927 elevate intracellular Ca2+ concentration, causing a reduction of the myocardial compliance and an increased diastolic blood pressure. Vessels also react to F90927 and contract in its presence. Binding of F90927 with the L-type Ca2+ channel presumably occurs in the vicinity of the transmembrane domains III and IV of the alpha1 subunit. F90927 exhibits no use dependence and interacts with Ca2+ channel inhibitors of all three known classes of channel modulators (dihydropyridines, phenylalkylamines, and benzothiazepines), suggesting that it is a member of a new class of Ca2+ channel modulators. Due to its adverse effects on blood pressure and vessel contraction, F90927 is not an ideal drug candidate. It has, however, some unique properties, which makes it a promising tool to study the function of the L-type Ca2+ channel.
Keller
Markus
M
Department of Physiology, University of Bern, Bern, Switzerland.
Pignier
Christophe
C
Egger
Marcel
M
Niggli
Ernst
E
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology*; D004970:Estrone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D015394:Molecular Structure; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; C510982:F90927; D004970:Estrone; D002118:Calcium