Biol. Pharm. Bull. 28(5) 811—816 (2005)

supply and demand for oxygen in the heart, and it is divided into Angina of Effort and Stable Angina depending on the cause of the anginal fit. The former is a situation of myocardial ischemia induced by a lack of oxygen, which is caused by an inability to increase blood flow due to coronary constriction. The latter is a situation of severe myocardial ischemia induced by coronary spasm or abnormal strain in periods of rest. Above all, in cases where anginal fit is frequent at daybreak or in the early morning, and a marked elevation of the ST segment from electrocardiography (ECG) is observed, it is called Variant Angina. ECG is used for an important diagnostic method for these diseases, because myocardial ischemia is closely reflected to changes on ECG such as elevation or depression in the ST segment. There are cases of these diseases where they occur alone or together; it cannot be classified simply, but regardless, a decrease in the oxygen demand and an increase in the myocardial blood flow are required in therapy. The clinical treatment of angina pectoris is mainly based on three groups of drugs, nitrates, b-adrenoceptor antagonists and calcium antagonists, which lead to the depression of oxygen consumption or the elevation of oxygen supply. The antianginal effect of calcium antagonists may be explained by their coronary dilatory effect (leading to the elevation of oxygen supply), cardio depressive effect (leading to the decrease of oxygen consumption) or the reduction of cardiac afterload according to antihypertensive effect. Based on their chemical structure, the compounds selective for slow calcium channels are divided to three subgroups; dihydropyridine (ex. nifedipine), benzothiazepine (ex. diltiazem) and phenylalkylamine (ex. verapamil). Recently, a second or third generation of dihydropyridine derivatives has been developed with the aim of providing greater vascular selectivity and a longer duration of action in order to allow a once-a-day dosage. A new 1,4-dihydropyridine derivative, lercanidipine (methyl 1,1-dimethyl-2-[N -(3,3-diphenylpropyl)-N-methylamino ethyl 2.6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate) (Fig. 1), synthesized at the Recordati Research Laboratory, is characterized by high vascular selectivity, a slow-onset and a long duration of the antihypertensive effect. These characteristics may qualify lercanidipine as a useful drug for the treatment of essential hypertension and angina pectoris. Fifty eight nations have approved this drug for clinical use as an antihypertensive, and clinical trials have progressed in Japan. Clinical trials of the antianginal effect have also progressed in Europe, and previous data reveal the great potential of this drug for clinical use. In this study, the possible target of the antianginal effect of lercanidipine was investigated using two models of angina pectoris with reference to nifedipine, benidipine and amlodipine. May 2005 Biol. Pharm. Bull. 28(5) 811—816 (2005) 811