Haemodynamic profile of an inhibitor of phosphodiesterase III, adibendan (BM 14.478): comparison with nitroprusside and dobutamine in conscious dogs.
1. This study was performed to investigate whether cardiac positive inotropic as well as peripheral vasodilator properties of adibendan contribute to its overall haemodynamic profile in conscious dogs. 2. Haemodynamic measurements were carried out in conscious chronically instrumented dogs after administration of adibendan, sodium nitroprusside or dobutamine. 3. The cardiovascular changes induced by adibendan (0.01 and 0.03 mg kg-1) resembled those of dobutamine (1.0-4.0 micrograms kg-1 min-1): left ventricular dP/dt60 (LV dP/dt60), stroke volume (SV) and cardiac output (CO) increased to a similar extent, but mean arterial pressure (MAP) and heart rate (HR) remained unchanged. 4. In contrast to dobutamine, higher doses of adibendan (0.1-1.0 mg kg-1) decreased MAP and LVEDP. These effects were of a similar magnitude to those observed following nitroprusside administration (0.5-12.5 micrograms kg-1 min-1). In contrast to nitroprusside, adibendan still showed additional effects on LV dP/dt60 and CO. 5. From these results, it is concluded that both the peripheral vasodilator and the cardiac positive inotropic action of adibendan contribute to its overall haemodynamic profile.
Dorszewski
A
A
Medizinische Forschung, Herz-/Kreislaufpharmakologie, Boehringer Mannheim GmbH, FRG.
Müller-Beckmann
B
B
Kling
L
L
Sponer
G
G
D000818:Animals; D001562:Benzimidazoles; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D000078183:Oxindoles; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001562:Benzimidazoles; D007093:Imidazoles; D000078183:Oxindoles; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D004280:Dobutamine; C053007:adibendan