Trans-
diclofurime has been shown to be a potent
calcium antagonist which resembles
verapamil in vitro and in vivo. Trans-
diclofurime was a potent antagonist of Ca2+-induced contractions in K+-depolarized taenia preparations from the guinea pig caecum (pA2 = 8.3 +/- 0.2), whereas the cis isomer was 50 times less active (pA2 = 6.6 +/- 0.1); the inhibitory effects of trans-
diclofurime were reversed noncompetitively by the Ca2+ channel activator
Bay K 8644. Trans-
diclofurime and
verapamil were equipotent inhibitors of electrically evoked contractions of guinea pig left atria preparations; the inhibitory effects were frequency dependent and cis-
diclofurime was 10 times less effective. Both
diclofurime isomers prolonged the effective refractory period at high concentrations, indicating that they also possess local anaesthetic properties. Trans-
diclofurime and
verapamil reduced blood pressure in pithed rats infused with
angiotensin II. Hypotensive effects were accompanied by
bradycardia and prolongation of PR intervals, leading to second-degree
atrioventricular block. The cis isomer was less potent.
Diclofurime is thus a very potent
calcium antagonist in heart and smooth muscle and has some additional membrane-stabilizing properties.