Cardiovascular effects of a novel calcium entry blocking and selective beta 1-adrenoceptor blocking agent, YM-16151-4, in anesthetized and conscious dogs.

Abstract

Cardiovascular effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in dogs. In anesthetized dogs, YM-16151-4 (0.01-1 mg/kg intravenously, i.v.) dose-dependently increased coronary blood flow (CBF) and decreased mean blood pressure (MBP), total peripheral resistance (TPR), dP/dtmax, double product, and left ventricular (LV) work without increasing heart rate (HR) and cardiac output (CO). YM-16151-4 increased vertebral blood flow as well as CBF, but had no effect on carotid, mesenteric, renal, and femoral blood flow. Coronary vasodilating activity of YM-16151-4 was also observed after intracoronary artery injection (i.a.). In anesthetized and vagotomized dogs, YM-16151-4 dose-dependently inhibited isoproterenol (0.2 micrograms/kg i.v.)-induced tachycardia and decrease in diastolic BP (DBP), with ED50 values of 0.039 and 0.52 mg/kg i.v., respectively. In conscious dogs, YM-16151-4 (0.1-1 mg/kg i.v.) produced a dose-dependent hypotensive effect with no effect on HR or PQ-interval. The hypotensive effect of YM-16151-4 (0.3 and 1 mg/kg i.v.) reached its maximum approximately 1-2 h after each dosing and lasted 6-8 h. These results suggest that YM-16151-4 actually behaves as a hybrid compound, combining calcium entry blocking and beta 1-adrenoceptor blocking activities, and that this compound could be a novel long-acting antianginal and antihypertensive agent.

• Authors: W Uchida, K Shibasaki, M Asano
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 19 Issue 1 Pg. 60-8 (Jan 1992) ISSN: 0160-2446 [Print] United States
• PMID: 1375689 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-Antagonists
• Calcium Channel Blockers
• Dihydropyridines
• Nitrophenols
• Vasodilator Agents
• YM 16151-1
• Atenolol
• Nifedipine

Topics

• Adrenergic beta-Antagonists (pharmacology)
• Anesthesia
• Animals
• Atenolol (pharmacology)
• Blood Pressure (drug effects)
• Calcium Channel Blockers (pharmacology)
• Coronary Circulation (drug effects)
• Coronary Vessels (drug effects)
• Dihydropyridines (pharmacology)
• Dogs
• Dose-Response Relationship, Drug
• Female
• Heart Conduction System (drug effects)
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Male
• Nifedipine (pharmacology)
• Nitrophenols (pharmacology)
• Vagotomy
• Vasodilator Agents (pharmacology)