Printed in U.S.A. Effects of a New Class of Calcium Antagonists, SR33557

SR33557 (fantofarone) and SR33805 are structurally novel cal-cium antagonists that bind selectively to the al-subunit of the L-type Ca channel at a site distinct from the classical 1,4-dihydropyndine, phenylalkylamine and benzothiazepine sites but in allostenc interactions with them. Blocking effects of fantofarone and SR33805 on the different types of voltage-activated Ca currents have been investigated with the whole-cell patch-clamp method in chick dorsal root ganglion neurons (for T-, L- and N-type currents) and in rat cerebellar Purkinje neurons (for P-type current) in primary culture. Neuro-nal L-type Ca channels are blocked totaily by fantofarone and 5R33805 in the tM range of concentration as in skeletal muscle and cardiac cells at a holding membrane potential of-80 mV. The sequence of efficacy is SR33805 (IC = 26 nM)> fantofarone (lC = 0.35 pM). N- and P-type channels are not very sensitive to fanto-farone and SR33805 (lC 5 MM). Th