Preventive effect of a new calcium antagonist, monatepil, on drug-induced ischaemic electrocardiographic changes in rats.
1. The preventive effects of monatepil, a new calcium antagonist with alpha 1-adrenoceptor blocking activity, on ischaemic electrocardiographic changes in rat models of vasospastic angina were evaluated and compared with those of the existing calcium antagonists (diltiazem, verapamil, nicardipine and nifedipine). 2. In order to assess the contribution of the alpha 1-adrenoceptor blocking action of monatepil to its anti-vasospastic action, the anti-ST depression effect of prazosin, an alpha 1-adrenoceptor blocker, was also examined. 3. Monatepil given orally (3-30 mg/kg) inhibited vasopressin (0.2 IU/kg, i.v.)-induced ST depression which is considered to indicate ischaemic electrocardiographic changes in a vasospastic angina. This effect of monatepil was more potent and long-lasting than that of diltiazem, and was similar to that of verapamil and nicardipine. At a dose of 30 mg/kg, monatepil produced a significant inhibition, even at 7 h after administration. 4. Monatepil given intravenously (0.3 mg/kg) exerted a significant inhibitory effect on methacholine (16 micrograms/kg, intracoronary arterial administration; i.c.a.)-induced ST elevation which seems to be caused by coronary vasospasm. This effect was more potent or equipotent to those of the existing calcium antagonists. 5. These results indicate that monatepil produces the preventive effect on the drug-induced ischaemic electrocardiographic changes in rats and suggest that monatepil may have potential for the treatment of vasospastic angina.
Yamamoto
T
T
Department of Pharmacology, Dainippon Pharmaceutical Co. Ltd, Osaka, Japan.
Nakatsuji
K
K
Hosoki
K
K
Karasawa
T
T
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003329:Coronary Vasospasm / Q000188:drug therapy*; D003988:Dibenzothiepins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004562:Electrocardiography / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014667:Vasopressins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D003988:Dibenzothiepins; D010879:Piperazines; D016210:Methacholine Chloride; D014667:Vasopressins; C067818:monatepil; D011224:Prazosin