Actions of the verapamil analogues, anipamil and ronipamil, against ischaemia‐induced arrhythmias in conscious rats

Abstract

Two analogues of verapamil, ronipamil and anipamil, were tested for their ability to reduce arrhythmias induced by occlusion of the left anterior descending coronary artery in conscious rats. Only anipamil (50 and 150 mg kg−1 orally) produced a statistically significant reduction in arrhythmias; it was most effective against ventricular fibrillation. Ronipamil at the same doses had limited antiarrhythmic actions. Only anipamil delayed the development of ECG signs of ischaemia, while both drugs reduced the magnitude of such changes. Anipamil has a more favourable ratio of antiarrhythmic to hypotensive effects when compared with verapamil.

The mechanism of action of calcium antagonists on arrhythmias in early myocardial ischaemia: studies with nifedipine and DHM9

“…Nifedipine did, however, delay the process of isch-aemia and infarction, as indicated by a delay in the development of pathognomic ECG signs. This pattern of response is almost exactly the same as the pattern described previously for other calcium antagonists in the conscious rat (Curtis et al, 1984;1985a;1986b;Curtis & Walker, 1986) and is not related to antiarrhythmic activity. No class of drug has been consistently found to reduce infarct size in rats with permanent coronary occlusion; we have argued that this is expected , given the paucity of collateral anastamoses in rat ventricles.…”

“…In previous studies we suggested that the antiarrhythmic effects of calcium antagonists occur entirely as a result of inhibition of Isi (Curtis et al, 1984;1985a;1986b;Curtis & Walker, 1986;Au et 8 1 '0 al., 1987), and that the site of action is most probably the ischaemic tissue. However, there appeared to be differences between the major classes of calcium antagonists, since we found that felodipine, a 1,4-dihydropyridine, had negligibile antiarrhythmic activity (Curtis et al, 1985a), whereas verapamil and other phenethylalkylamines (Curtis et al, 1984; I h 1986b; Curtis & Walker, 1986;Au et al, 1987) were effective, yet both classes of drugs produced similar reductions in blood pressure.…”

“…The other perfusion fluid constituents were standard (Krebs-Henseleit solution) with the exception of CaCI2, which was 0.7 mm to give a developed pressure of approximately 50% of maximum as described previously (Curtis et al, 1984). The apparatus used for the delivery of perfusion fluid permitted the generation of cumulative concentration-response data from individual preparations, owing to its facility for rapid switching between fluid storage vessels (Curtis et al, 1986b). Excitability was measured after stabilization, followed by measurement of the effects of nifedipine and DHM9 on developed pressure by the construction of six-point concentration-response curves, in the manner described previously (Curtis & Walker, 1986 (Mainland et al, 1956).…”

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

“…Anipamil had a stronger antiarrhythmic than hypotensive effect compared to verapamil in rats [280]. Anipamil pretreatment proved to be protective against LAD ligation induced functional (monitored by ECG signs) and biochemical (creatine kinase loss) damage in rats.…”

“…There are several animal studies showing the antiarrhythmic action of anipamil in rats [280]- [282] and also in pigs [283]. Anipamil had a stronger antiarrhythmic than hypotensive effect compared to verapamil in rats [280].…”