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.
AuthorsM Spedding, M Gittos, A K Mir
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 9 Issue 4 Pg. 461-8 (Apr 1987) ISSN: 0160-2446 [Print] UNITED STATES
PMID2438509 (Publication Type: Journal Article)
Chemical References
  • Calcium Channel Blockers
  • Neuromuscular Depolarizing Agents
  • Oximes
  • diclofurime
  • Potassium
  • Animals
  • Calcium Channel Blockers
  • Colon (drug effects)
  • Decerebrate State
  • Guinea Pigs
  • Heart (drug effects)
  • In Vitro Techniques
  • Male
  • Muscle, Smooth (drug effects)
  • Myocardial Contraction (drug effects)
  • Neuromuscular Depolarizing Agents
  • Oximes (pharmacology)
  • Papillary Muscles (drug effects)
  • Potassium (pharmacology)
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Stereoisomerism

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