Antihypertensive effects of intravenous administration of benidipine hydrochloride and some other calcium antagonists in conscious, spontaneously hypertensive rats

Arzneimittelforschung. 1988 Nov;38(11A):1691-4.

Abstract

The antihypertensive effect of intravenously administered (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was examined in conscious, spontaneously hypertensive rats (SHR) and comparatively evaluated with those of nifedipine, nicardipine, nitrendipine, nisoldipine, verapamil and diltiazem. When nifedipine (10 and 100 micrograms/kg), nicardipine (10 and 100 micrograms/kg), nitrendipine (10 and 100 micrograms/kg), verapamil (100 and 1000 micrograms/kg) and diltiazem (100 and 1000 micrograms/kg) were intravenously administered to SHR, at their lower doses, only transient decreases of blood pressure were observed and, even at their higher doses, decreased blood pressures returned to the initial levels after 80 to 120 min. Nisoldipine at 10 micrograms/kg (i.v.) decreased the blood pressure (by 23 mmHg), lasting for 100 to 120 min, and the antihypertensive effect of 100 micrograms/kg (i.v.) of it (by 63 mmHg) lasted for longer than 240 min though a tendency of blood pressure to recover was observed. The peak effects of these 6 calcium antagonists were observed 1 min after the drug injection. When KW-3049 (1, 3, 10 and 30 micrograms/kg i.v.) was administered, a dose-dependent decrease of blood pressure (by 23 to 67 mmHg) was observed. The effect of KW-3049 was longer than those of the above 6 calcium antagonists, including nisoldipine. The maximal effects were attained 10 to 30 min after the drug injection and the decreased blood pressure did not return to an initial level even 180 min (at 1 and 3 micrograms/kg) and 240 min (at 10 and 30 micrograms/kg) after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use*
  • Diltiazem / administration & dosage
  • Diltiazem / pharmacology
  • Diltiazem / therapeutic use
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects
  • Hypertension / drug therapy*
  • Injections, Intravenous
  • Male
  • Nicardipine / administration & dosage
  • Nicardipine / pharmacology
  • Nicardipine / therapeutic use
  • Nifedipine / administration & dosage
  • Nifedipine / analogs & derivatives*
  • Nifedipine / pharmacology
  • Nifedipine / therapeutic use
  • Nisoldipine
  • Nitrendipine / administration & dosage
  • Nitrendipine / pharmacology
  • Nitrendipine / therapeutic use
  • Rats
  • Rats, Inbred SHR
  • Verapamil / administration & dosage
  • Verapamil / pharmacology
  • Verapamil / therapeutic use

Substances

  • Antihypertensive Agents
  • Calcium Channel Blockers
  • benidipine hydrochloride
  • Nisoldipine
  • Nitrendipine
  • Verapamil
  • Nicardipine
  • Diltiazem
  • Nifedipine