Antihypertensive effects of CS-905, a novel dihydropyridine Ca++ channel blocker

Jpn J Pharmacol. 1989 Sep;51(1):57-64. doi: 10.1254/jjp.51.57.

Abstract

CS-905 is a novel dihydropyridine calcium blocker. A single oral administration of CS-905 or nicardipine at doses of 0.3-3.0 mg/kg produced a dose-dependent reduction of blood pressure in conscious SHR. CS-905, when administered orally in conscious SHR, was more than 3 times as potent as nicardipine. Unlike the hypotensive effect of nicardipine, that of CS-905 has a gradual onset and is long-lasting, with little increase in heart rate. An intravenous administration of CS-905 also produced a hypotension with a slow onset and long duration in SHR, but CS-905 was 3 times less potent than nicardipine by intravenous administration. This difference may be attributed to the first pass effect, which was associated with nicardipine but not with CS-905. The blood pressure lowering effects of CS-905 was most potent in DOCA-salt hypertensive rats, followed by SHR, RHR and normotensive rats, in this order. CS-905 is expected to be an antihypertensive agent that is effective on a once a day regimen in clinical settings.

MeSH terms

  • Anesthesia
  • Animals
  • Antihypertensive Agents*
  • Aorta / drug effects
  • Azetidinecarboxylic Acid / analogs & derivatives
  • Azetidinecarboxylic Acid / pharmacology*
  • Azetines / pharmacology*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Desoxycorticosterone
  • Dihydropyridines / pharmacology*
  • Heart Rate / drug effects
  • Hypertension / chemically induced
  • Hypertension / drug therapy
  • Hypertension / physiopathology
  • Hypertension, Renal / drug therapy
  • Hypertension, Renal / physiopathology
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Nephrectomy
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred Strains

Substances

  • Antihypertensive Agents
  • Azetines
  • Calcium Channel Blockers
  • Dihydropyridines
  • Desoxycorticosterone
  • Azetidinecarboxylic Acid
  • azelnidipine