Antagonism of the effect of isoprenaline on heart rate by pilocarpine.

1 The interaction of pilocarpine and isoprenaline on heart rate was investigated in the spontaneously beating, right isolated atrium of the rat.2 The log dose-effect curve of isoprenaline, measured in the presence of various concentrations of pilocarpine, was not modified when the concentration of the latter did not exceed 10(-6)M even though significant slowing of the heart had occurred. At concentrations higher than 10(-6)M a rapid but graded shift to the right of isoprenaline response curves occurred so that at pilocarpine 10(-5)M the pD(2) of isoprenaline was reduced from 11 to 3.3; cocaine slightly reduced this antagonism.3 It is concluded that pilocarpine antagonizes isoprenaline by some mechanism which is not of the simple competitive type.