Effect of KRN2391, a novel vasodilator, on various experimental anginal models in rats.
The antianginal effect of KRN2391, N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate, on various anginal models in rats was compared with those of nifedipine and nicorandil. Angina pectoris was induced by methacholine or isoproterenol, and the change in the ST-segments in the electrocardiogram (ECG) was used as the parameter to indicate angina pectoris. The intracoronary administration of methacholine (3 micrograms) produced an elevation in the ST-segment of the ECG. This ST-elevation was inhibited by the intravenous administration of KRN2391 (30 and 100 micrograms/kg), nifedipine (100 and 300 micrograms/kg) and nicorandil (1000 and 3000 micrograms/kg). The administration of isoproterenol (10 micrograms/kg/min, i.v.) produced a depression of the ST-segment of the ECG. The intravenous administration of KRN2391 (100 micrograms/kg), nifedipine (100 micrograms/kg) and nicorandil (3000 micrograms/kg) inhibited the ECG changes induced by isoproterenol. These results suggest that KRN2391 exerts a potent protective effect on angina pectoris models compared with nifedipine and nicorandil. KRN2391 appears to be useful as an antianginal drug.
Harada
K
K
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Fukata
Y
Y
Miwa
A
A
Kaneta
S
S
Fukushima
H
H
Ogawa
N
N
D000787:Angina Pectoris / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects*; D007275:Injections, Intravenous; D007545:Isoproterenol; D008297:Male; D016210:Methacholine Chloride; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D020108:Nicorandil; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D011725:Pyridines; D014665:Vasodilator Agents; D016210:Methacholine Chloride; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D009536:Niacinamide; D020108:Nicorandil; D009543:Nifedipine; D007545:Isoproterenol