title: Effects of CP-060S, a novel cardioprotective drug, in the methacholine-induced ECG change model in rats.
abstract: We compared the antianginal effect of CP-060S, a novel cardioprotective drug with Na+ and Ca2+ overload-preventing activity as well as Ca2+ 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-060S (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-060S 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-060S given i.v. could inhibit the ST-elevation with less haemodynamic changes than diltiazem. In conclusion, CP-060S exerted a more potent and sustained protection against myocardial ischemia evoked by methacholine than diltiazem. The characteristics of the effects of CP-060S observed here suggest that this drug may be a desirable drug for the treatment of vasospastic angina.
authors.affiliation: Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotembashi, Shizuoka 412-8513, Japan. fukazawamsn@chugai-pharm.cp.jp
authors.forename: M
authors.initials: M
authors.lastname: Fukazawa
authors.forename: Y
authors.initials: Y
authors.lastname: Adachi
authors.forename: M
authors.initials: M
authors.lastname: Akima
authors.forename: J I
authors.initials: JI
authors.lastname: Imagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: O
authors.initials: O
authors.lastname: Kuromaru
authors.forename: K
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology; D002794:Choline / Q000493:pharmacokinetics; D003331:Coronary Vessels / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology / Q000627:therapeutic use; D004562:Electrocardiography / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D053778:Thiazolidines; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C104781:CP 060S; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D013844:Thiazoles; D053778:Thiazolidines; D014665:Vasodilator Agents; D004110:Diltiazem; D002794:Choline