Haemodynamic effects of lercanidipine in anaesthetized open-chest dogs.
In this study, the haemodynamic effects of lercanidipine (CAS 132866-11-6, Rec 15/2375) in anaesthetized open-chest dogs were investigated in comparison with nitrendipine. Intravenously administered lercanidipine induced a dose-related, long-lasting reduction in systemic and coronary vascular resistances, with concomitant decrease in arterial blood pressure and increase in coronary blood flow. The hypotensive ED25 was 6.1 micrograms/kg and 4.2 micrograms/kg (decrease of mean blood pressure and of total peripheral resistances, respectively) and the ED50 on coronary vasodilation, 4.8 micrograms/kg 7.8 micrograms/kg (increase of coronary blood flow and decrease in coronary vascular resistances, respectively). The time-course of the haemodynamic effects was investigated after administration of 5 micrograms/kg. A slow onset of haemodynamic vasodilation and long-lasting activity were observed, since peak effects on mean blood pressure and coronary blood flow occurred at 20 and 30 min after the administration, respectively, and the effects on systemic and coronary resistances were still significant at 30 and 150 min after administration, respectively. A reflex, non-dose-dependent increase in heart rate was observed after the administration of 10 and 30 micrograms/kg, which was absent with the 5 micrograms/kg dose. As far as cardiac contractility was concerned, the contractile index dP/dtmax and dP/dt/P were analyzed. In the dose-response study, dP/dtmax was practically not affected. In the time-course study, dP/dtmax was not modified after administration of 5 micrograms/kg, and dP/dt/P showed a slight but long-lasting increase. Haemodynamic investigation confirmed in vivo the high vascular selectivity of lercanidipine and a lack of sympathetic reflex activation at vasodilating doses.
Sironi
G
G
Pharmaceutical R&D Division, Recordati S.p.A., Milan, Italy.
Montagna
E
E
Greto
L
L
Leonardi
A
A
Testa
R
R
D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology; D013997:Time Factors
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009568:Nitrendipine; C060343:lercanidipine