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New photodegradation products of nifedipine (1) have been isolated. They were found in tablets dispensed in the pulverized form by hospitals. 1 decomposed concurrently into six components after storage of 30 days under exposure to normal room light. The main photoproduct was a nitroso derivative (2) and others were minor. Preparative thin-layer chromatography has been used to isolate the six photodegradation products. The chemical structures of these isolated compounds were identified or estimated by comparison with authentic samples and/or using UV, IR, 1H NMR, mass spectroscopy, melting point determination, and elementary analysis. From these analyses, it was found that 1 was converted into a cis-azoxy derivative (4), a trans-azoxy derivative (5), a N,N'-dioxide derivative (6) and a lactam derivative (7) in addition to 2 and a nitro derivative (3). Furthermore, it is proposed that 2 is mainly responsible for the formation of these new products (4-7) by photochemical condensation.

The effect of bunitrolol, a beta-adrenergic blocking agent having intrinsic sympathomimetic activity, on ischemic myocardial metabolism was examined in anesthetized dog hearts. Ischemia was induced by ligating the left anterior descending coronary artery for 3 or 30 min. Bunitrolol (0.3 or 1.0 mg/kg of body weight) was injected intravenously 5 min before the onset of ischemia. Ischemia reduced myocardial high-energy phosphate levels and changed the levels of glycolytic intermediates. Bunitrolol at a dose of 0.3 mg/kg significantly decreased heart rate, whereas the drug at a dose of 1.0 mg/kg did not. This result suggests that intrinsic sympathomimetic activity is observed only at a high dose of bunitrolol. Pretreatment with bunitrolol at 0.3 but not 1.0 mg/kg attenuated the myocardial metabolic changes caused by 3 min of ischemia. After 30 min of ischemia, a beneficial effect of bunitrolol on the ischemic myocardium was not observed. These results suggest that bunitrolol may lessen the ischemic influence on the myocardium in the early stage of ischemia and that intrinsic sympathomimetic action may not have a beneficial effect on the ischemic myocardium.

The effect of amosulalol, a combined alpha 1- and beta-adrenoceptor-blocking agent, on changes in myocardial energy and carbohydrate metabolism during ischemia was studied. Ischemia was induced by ligating the left anterior descending coronary artery for 3 or 30 min during open-chest surgery in anesthetized dogs. The myocardial energy stores were depleted, and the levels of glycolytic intermediates were altered by 3 and 30 min of ischemia, indicating that anaerobic myocardial metabolism had occurred. Amosulalol (0.3 or 1 mg.kg-1) was injected intravenously 5 min before ischemia. Pretreatment with amosulalol, particularly at a dose of 0.3 mg.kg-1, reduced the myocardial energy depletion and the alteration of carbohydrate metabolism induced by ischemia. This result indicates that amosulalol can reduce ischemic influences on the myocardium.

The effect of NCO-700 (1), a protease inhibitor, on subcellular distribution of lysosomal enzymes was studied in the ischemic perfused rat heart. Ischemia was induced by lowering the afterload pressure of the working heart preparation. The subcellular distribution of lysosomal enzymes was estimated by the ratio of the activities of cathepsin D, beta,N-acetylglucosaminidase, and acid phosphatase in the cytoplasm to the total enzyme activities. Ischemia caused subcellular redistribution of lysosomal enzymes from the lysosomes to the cytoplasm, indicating the rupture of lysosomes. Compound 1 (1.75 x 10(-4) M) was provided for the heart 5 min before the onset of ischemia. Compound 1 appeared to inhibit the rupture of lysosomes being caused by ischemia. The mechanism by which 1 protects the myocardium against ischemic injury may involve the inhibition of lysosomal rupture in the ischemic myocardium.