EFFECTS OF A NEW CLASS OF CALCIUM-ANTAGONISTS, SR33557 (FANTOFARONE) AND SR33805, ON NEURONAL VOLTAGE-ACTIVATED CA++ CHANNELS

SR33557 (fantofarone) and SR33805 are structurally novel calcium antag onists that bind selectively to the alpha 1-subunit of the L-type Ca+ channel at a site distinct from the classical 1,4-dihydropyridine, ph enylalkylamine and benzothiazepine sites but in allosteric interaction s with them. Blocking effects of fantofarone and SR33805 on the differ ent types of voltage-activated Ca++ currents have been investigated wi th the whole-cell patch-clamp method in chick dorsal root ganglion neu rons (for T-, L- and N-type currents) and in rat cerebellar Purkinje n eurons for P-type current) in primary culture. Neuronal L-type Ca++ ch annels are blocked totally by fantofarone and SR33805 in the mu M rang e of concentration as in skeletal muscle and cardiac cells at holding membrane potential of -80 mV. The sequence of efficacy is SR33805 (IC5 0 = 26 nM) > fantofarone (IC50 = 0.35 mu M). N- and P-type channels ar e not very sensitive to fanto-farone and SR33805 (IC50 similar to 5 mu M). The T-type channel is not affected by these drugs.