Preventive effect of monatepil on thromboxane A2 agonist-induced myocardial ischemia in rats
Yamamoto, T.; Hosoki, K.; Kikuta, C.; Karasawa, T.
Arzneimittel-Forschung 44(6): 712-714
1994
ISSN/ISBN: 0004-4172 PMID: 8053969 Document Number: 438426
Antianginal effects of monatepil (((+-)-N-(6,11-dihydrodibenzo(b,e)thiepin-11-yl)-4-(4-fluorophenyl)-1piperazinebutanamide)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,9-alpha,11-alpha,13E,15(S))-9,11-(methano-epoxy)prosta-5,13-dien-1-oic acid) (10 mu-g/kg), a stable thromboxane A-2 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.