Calcium antagonist properties of diclofurime isomers. I. Functional aspects.
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.
D000818:Animals; D002121:Calcium Channel Blockers; D003106:Colon / Q000187:drug effects; D003655:Decerebrate State; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents; D010091:Oximes / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D009467:Neuromuscular Depolarizing Agents; D010091:Oximes; C010826:diclofurime; D011188:Potassium