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Effects of CP‐060S, a novel cardioprotective drug, in the methacholine‐induced ECG change model in rats
Author(s) -
Fukazawa Masanori,
Adachi Yuichiro,
Akima Michitaka,
Imagawa Junichi,
Suzuki Yoshiyuki,
Kuromaru Osamu,
Tamura Kazuhiko
Publication year - 2001
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1046/j.1472-8206.2001.00014.x
Subject(s) - diltiazem , medicine , methacholine , angina , blood pressure , heart rate , cardiology , anesthesia , hemodynamics , ischemia , pharmacology , st segment , myocardial infarction , calcium , lung , respiratory disease
We compared the antianginal effect of CP‐060 S , a novel cardioprotective drug with Na + and Ca 2+ overload‐preventing activity as well as Ca 2+ channel antagonistic activity, with that of diltiazem, in an experimental model of vasospastic angina induced by methacholine in anaesthetized rats. Intra‐aortic injection of methacholine at the coronary ostium provoked the ST‐segment elevation of the electrocardiogram (ECG), indicating myocardial ischemia. CP‐060 S (3, 5 and 10 mg/kg, i.d.) significantly and dose‐dependently suppressed the methacholine‐induced ST‐elevation, with the duration of action being at least 3 h at the highest dose. In addition, CP‐060 S at 3 mg/kg could inhibit the ST‐elevation without producing significant changes in blood pressure, heart rate or rate‐pressure product (RPP). In contrast, diltiazem (10 and 30 mg/kg, i.d.) significantly decreased the RPP, a significant suppression of the ST‐elevation could only be achieved at the highest dose and its duration of action was about 2 h. Similar results were obtained with i.v. administration of the drugs, i.e. CP‐060 S given i.v. could inhibit the ST‐elevation with less haemodynamic changes than diltiazem. In conclusion, CP‐060 S exerted a more potent and sustained protection against myocardial ischemia evoked by methacholine than diltiazem. The characteristics of the effects of CP‐060 S observed here suggest that this drug may be a desirable drug for the treatment of vasospastic angina.