Calcium-antagonist effects of norbormide on isolated perfused heart and cardiac myocytes of guinea-pig: a comparison with verapamil
Article first published online: 3 FEB 2009
1996 British Pharmacological Society
British Journal of Pharmacology
Volume 120, Issue 1, pages 19–24, January 1997
How to Cite
Bova, S., Cargnelli, G., D'Amato, E., Forti, S., Yang, Q., Trevisi, L., Debetto, P., Cima, L., Luciani, S. and Padrini, R. (1997), Calcium-antagonist effects of norbormide on isolated perfused heart and cardiac myocytes of guinea-pig: a comparison with verapamil. British Journal of Pharmacology, 120: 19–24. doi: 10.1038/sj.bjp.0700876
- Issue published online: 3 FEB 2009
- Article first published online: 3 FEB 2009
- (Received May 20, 1996, Revised September 15, 1996, Accepted September 27, 1996)
- isolated perfused heart;
- L-type calcium current
Cardiac effects of norbormide and verapamil were compared in single ventricular myocytes, right atria, and Langendorff perfused hearts isolated from guinea-pigs.
In ventricular myocytes, norbormide 50 μm inhibited the peak calcium current (ICa) by 49.6±3.9% without altering the shape of the current-voltage relationship; verapamil 1 μm inhibited ICa by 83.2±3.3%. Neither norbormide nor verapamil affected ICa at the first beat after a 3 min quiescence period; during repeated depolarizations, both drugs cumulatively blocked ICa (use-dependence), with time constants of 23.0±7.0 s for norbormide and 91.3±8.4 s for verapamil.
In constant-flow perfused hearts electrically driven at 2.5 Hz or 3.3 Hz, both norbormide and verapamil concentration-dependently decreased ventricular contractility (dP/dtmax), atrio-ventricular (AV) conduction velocity and coronary pressure. Intraventricular conduction velocity was slightly decreased by norbormide but not by verapamil. At an equivalent change in AV conduction, norbormide depressed heart contractility less than verapamil. The effects of norbormide on AV conduction, intraventricular conduction, and contractility were frequency-dependent. Furthermore, the curves correlating the mechanical and electrical effects of norbormide at the two frequencies used were apparently coincident, while those of verapamil were clearly separated.
In spontaneously beating right atria, norbormide and verapamil decreased the frequency of sinus node (SA) in a concentration-dependent way. At an equivalent effect on the AV conduction, norbormide exerted a greater effect on sinus frequency than verapamil.
These results indicate that in guinea-pig heart norbormide has the pharmacological profile of a Ca-antagonist with strong electrophysiological properties. In comparison with verapamil, norbormide is more selective on SA and AV node tissues and exerts a weaker negative inotropic effect on ventricles. In principle, this pattern of effects may be an advantage in treating supraventricular tachyarrhythmias in patients with heart failure. The effect of norbormide on intraventricular conduction may represent an additional antiarrhythmic mechanism.
British Journal of Pharmacology (1997) 120, 19–24; doi:10.1038/sj.bjp.0700876