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 α₁ 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.