Antianginal effects of the new calcium antagonist benidipine hydrochloride in anesthetized rats and spontaneously hypertensive rats. Electrocardiographic study.

Abstract

Antianginal effects of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) in various experimental angina-pectoris models (anesthetized rats, spontaneously hypertensive rats (SHR] were compared with those of nifedipine, propranolol and hydralazine. Furthermore, the effects of these drugs on the pressure-rate product were evaluated. 1. Vasopressin test (SHR): The administration of KW-3049 at 10 micrograms/kg (i.v.) developed an inhibitory effect comparable to that of nifedipine at 200 micrograms/kg (i.v.) against the ischemic ECG changes caused by the intravenous administration of vasopressin at 1 U/kg. The effects of KW-3049 at 3 and 10 mg/kg (p.o.) lasted for 8 h or more. 2. Coronary occlusion test (rat): The rise of T-wave of epicardial ECG following ligation of coronary artery was inhibited by the administration of KW-3049 at doses of 30 and 100 micrograms/kg i.v. Nifedipine at dose of 200 micrograms/kg i.v. was slightly effective. 3. Isoproterenol (isoprenaline) test (rat): The fall of ST in ECG by the continuous infusion of isoprenaline (10 micrograms/kg/min) was almost completely prevented by propranolol (500 micrograms/kg i.v.). Also, KW-3049 (200 micrograms/kg i.v.) and nifedipine (200 micrograms/kg i.v.) significantly inhibited the decline of ST, in which the former was more effective than the latter. 4. Anoxia test (SHR): The fall of ST and rise of T-wave of ECG, induced by stopping artificial respiration of gallamine-immobilized SHR, were suppressed by the administration of KW-3049 at doses of 10 and 30 micrograms/kg i.v.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: A Karasawa, K Kubo, K Shuto, T Oka, N Nakamizo
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 38 Issue 11A Pg. 1702-7 (Nov 1988) ISSN: 0004-4172 [Print] Germany
• PMID: 3219144 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Calcium Channel Blockers
• benidipine hydrochloride
• Vasopressins
• Hydralazine
• Propranolol
• Nifedipine
• Isoproterenol

Topics

• Angina Pectoris (drug therapy)
• Animals
• Blood Pressure (drug effects)
• Calcium Channel Blockers (pharmacology, therapeutic use)
• Coronary Circulation (drug effects)
• Electrocardiography
• Heart Rate (drug effects)
• Hydralazine (pharmacology, therapeutic use)
• Isoproterenol (administration & dosage)
• Male
• Nifedipine (analogs & derivatives, pharmacology, therapeutic use)
• Propranolol (pharmacology, therapeutic use)
• Rats
• Rats, Inbred SHR
• Rats, Inbred Strains
• Vasopressins (administration & dosage)