title: The hemodynamic effects of lacidipine in anesthetized dogs: comparison with nitrendipine, amlodipine, verapamil, and diltiazem.
abstract: The hemodynamic effects of lacidipine in anesthetized, open-chest dogs were compared with those of nitrendipine, amlodipine, verapamil and diltiazem. Lacidipine administered intravenously induced dose-related, long-lasting reductions in systemic and coronary vascular resistance with corresponding increases in aortic flow and coronary blood flow. The hypotensive effect (ED25 for mean blood pressure reduction = 0.006 mg/kg) was still significant 120 min after administration with all doses tested. Nitrendipine was equipotent with lacidipine in reducing the mean blood pressure (ED25 = 0.005 mg/kg), but its effect was shorter acting (significant effect at 120 min only with the highest dose tested). Amlodipine caused a marked and long-lasting hypotension though at higher doses than lacidipine (ED25 = 0.50 mg/kg). Short-lasting hypotensive responses were also detected with verapamil (ED25 = 0.1 mg/kg) and diltiazem (ED25 = 0.12 mg/kg). A reflex increase in heart rate was observed with lacidipine, nitrendipine, and amlodipine, whereas verapamil and diltiazem showed a dose-related bradycardia. No effect on AV conduction was observed with lacidipine and nitrendipine, whereas amlodipine, verapamil, and diltiazem produced second- to third-degree AV block at the highest doses tested. Lacidipine and nitrendipine caused a reflex increase in contractile index at all doses, whereas amlodipine was more similar to verapamil since a marked decrease in contractile index was detected at the highest dose. Diltiazem was practically devoid of negative inotropic effect.
authors.affiliation: Glaxo Research Laboratories, Verona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Quartaroli
authors.forename: F
authors.initials: F
authors.lastname: Gambini
authors.forename: G
authors.initials: G
authors.lastname: Tarter
authors.forename: D
authors.initials: D
authors.lastname: Micheli
authors.forename: D G
authors.initials: DG
authors.lastname: Trist
authors.forename: G
authors.initials: G
authors.lastname: Gaviraghi
mesh_terms: D017311:Amlodipine; D000758:Anesthesia; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017311:Amlodipine; C060285:lacidipine; D009568:Nitrendipine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine