Naunyn-Schmiedeberg's archives of pharmacology. vol:337 issue:4 pages:454-8
A single glass micropipette voltage clamp technique with intracellular dialysis was used to study the effects of the trapidil derivatives AR 12-456 and AR 12-463 on Ca channel currents carried by Ba2+ in isolated ventricular cells from mice hearts. Inspite of a more potent inhibition of the cAMP phosphodiesterase from heart (Bartel et al. 1985) a reversible Ca channel blocking action of both compounds could be observed. The concentration of half maximal block was calculated to about 50 mumol/l for both derivatives tested. Neither a shift in the current-voltage relationships nor a significant change in the potential for half maximal activation was found. The maximal Ba2+-conductance was reduced. The steady state inactivation was shifted towards more negative potentials by application of 100 mumol/l AR 12-463. The decay of the Ba currents was accelerated in the range of the applied test potentials between -20 and +20 mV. It is concluded that the new trapidil derivatives with more potent inhibitory action on cardiac phosphodiesterase than trapidil can block myocardial Ca channels.