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Cardiovascular effects of OPC-13340, a potent, long-acting 1,4-dihydropyridine calcium channel blocker, in dogs.

Abstract
The cardiovascular effects of OPC-13340, a newly developed 1,4-dihydropyridine calcium channel blocker, were examined in several canine preparations. In conscious normotensive and DOCA-salt hypertensive dogs, OPC-13340, at doses of 10 to 30 micrograms/kg, i.v., and 0.3 to 3 mg/kg, p.o., exerted an hypotensive action in a dose-dependent manner. The hypotensive action of OPC-13340 was longer lasting and more potent than that of nicardipine and nifedipine. In conscious, normotensive instrumented dogs, OPC-13340, at doses of 1 and 3 mg/kg, p.o., dose-dependently decreased total peripheral resistance and mean blood pressure and increased heart rate, cardiac output and left ventricular contractility. In anesthetized open-chest dogs, OPC-13340, at doses of 1 to 30 micrograms/kg, i.v., increased coronary blood flow and decreased mean blood pressure, heart rate, coronary vascular resistance, arteriovenous oxygen difference and myocardial oxygen consumption. In contrast to OPC-13340, nicardipine did not change the myocardial oxygen consumption. From these results it was concluded that OPC-13340 lowered blood pressure and improved coronary circulation in dogs and that the duration of these actions was longer lasting than that of nifedipine and nicardipine. These actions of OPC-13340 may be useful in the treatment of hypertension and angina pectoris.
AuthorsT Mori, N Nakayama, M Ohura, K Ikezono, S Kinoshita, M Kamata, T Hosokawa, S Yamashita, Y Yabuuchi
JournalArchives internationales de pharmacodynamie et de therapie (Arch Int Pharmacodyn Ther) 1993 Jan-Feb Vol. 321 Pg. 41-56 ISSN: 0003-9780 [Print] Belgium
PMID8323415 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Calcium Channel Blockers
  • Dihydropyridines
  • Desoxycorticosterone
  • pranidipine
  • Nicardipine
  • Nifedipine
Topics
  • Anesthesia
  • Animals
  • Blood Pressure (drug effects)
  • Calcium Channel Blockers (pharmacology)
  • Desoxycorticosterone
  • Dihydropyridines (pharmacology)
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Heart Rate (drug effects)
  • Hemodynamics (drug effects)
  • Hypertension (chemically induced, drug therapy, physiopathology)
  • Male
  • Myocardium (metabolism)
  • Nicardipine (pharmacology)
  • Nifedipine (pharmacology)
  • Oxygen Consumption (drug effects)

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