Piprofurol is a
benzofuran chalcon derivative. It was studied under various experimental conditions which allow the recognition of
calcium antagonistic activity.
Piprofurol inhibited in a concentration-dependent manner the
calcium-induced contractions in isolated
potassium depolarized preparations of rat aorta (pA2: 9.29) and relaxed the K+-induced contraction of the dog coronary artery and the rabbit basilar artery (IC's 50: 2 10(-8) M; 3 10(-9) M).
Piprofurol also inhibited
noradrenaline-induced vascular smooth muscle contractions but the antagonism was clearly noncompetitive and the contractions induced were altered by concentrations two orders of magnitude higher than the concentration inhibiting
calcium-induced contractions.
Calcium antagonism was demonstrated in cardiac muscle:
calcium mediated slowly rising action potentials were evoked in partially depolarized guinea-pig papillary muscle by electrical stimulation in the presence of
isoprenaline.
Piprofurol decreased the rate of rise of these slow action potentials. The inhibitory effect was reversed by an elevation of the
calcium concentration in the bath fluid.
Piprofurol exerts a negative inotropic effect (IC50: 5 10(-6) M) on guinea-pig papillary muscle. The ratio IC50 inotropic action/IC50 relaxant activity was 230, i.e. higher than that obtained with
verapamil or
diltiazem, and near that observed for
cinnarizine. The pharmacological profile from in vivo dog experiments is in agreement with its in vitro properties: coronary sinus blood flow was increased and heart rate decreased. These effects suggested a potentially anti-ischaemic activity. This is confirmed in anaesthetized dogs, where
piprofurol reduced the epicardial ST-segment elevation following coronary artery occlusion, and in isolated heart preparations, where it decreased the leakage of LDH during periods of
anoxia and reoxygenation.