Preventive effect of monatepil on thromboxane A2 agonist-induced myocardial ischemia in rats.
Antianginal effects of monatepil ([(+-)-N-(6,11-dihydrodibenzo[b,e]thiepin-11-yl)-4-(4-fluor ophenyl)-1-piperazinebutanamide]monomaleate, AJ-2615, CAS 10337-41-9), a new calcium antagonist, were evaluated in experimentally induced myocardial ischemia in anesthetized rats and compared with those of diltiazem. Ischemic electrocardiogram change (ST elevation) and reduction of myocardial tissue oxygen tension were induced by intracoronary arterial administration of U-46619 ((5Z,9a,11a,13E,15(S))-9,11-(methano-epoxy)prosta-5,13-di en-1-oic acid) (10 micrograms/kg), a stable thromboxane A2 agonist. The ST elevation induced by U-46619 was significantly prevented by monatepil pretreatment (0.1 mg/kg i.v.), and to a lesser extent by diltiazem (0.3 mg/kg i.v.). Moreover, the decrease in myocardial tissue oxygen tension at the time of ST elevation after U-46619 was inhibited by monatepil pretreatment (0.3 mg/kg i.v.). These results indicate that monatepil exerts a more potent preventive effect against U-46619-induced myocardial ischemic changes than diltiazem and suggest that monatepil has potential for treating vasospastic angina.
Yamamoto
T
T
Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Hosoki
K
K
Kikuta
C
C
Karasawa
T
T
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003988:Dibenzothiepins / Q000627:therapeutic use*; D004110:Diltiazem / Q000627:therapeutic use; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
D002121:Calcium Channel Blockers; D003988:Dibenzothiepins; D010879:Piperazines; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D004110:Diltiazem; C067818:monatepil