LONG-TERM EFFECTS OF MOLSIDOMINE ON EXERCISE TOLERANCE IN PATIENTS WITH EXERTIONAL ANGINA PECTORIS

• Published in: JAPANESE CIRCULATION JOURNAL Vol. 47; no. 12; pp. 1398 - 1405
• Main Authors: KINOSHITA, MASAHIKO, SAWAMURA, MATSUHIKO, MOTOMURA, MASAKAZU, TAKAYAMA, YUKIO, KAWAGUCHI, YOSHIHIRO, KAWAKITA, SEIICHI
• Format: Journal Article
• Language: English
• Published: Kyoto The Japanese Circulation Society 01.01.1983; Japanese Circulation Society
• Subjects: Aged; Angina pectoris; Angina Pectoris - drug therapy; Angina Pectoris - physiopathology; Antianginal agents. Coronary vasodilator agents; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular system; Drug Tolerance; Electrocardiography; Exercise Test; Heart Rate - drug effects; Humans; Medical sciences; Middle Aged; Molsidomine; Oxadiazoles - pharmacology; Pharmacology. Drug treatments; Physical Exertion; Sydnones - administration & dosage; Sydnones - pharmacology; Treadmill test; Physical exercise; Chemotherapy; Treatment; Tolerance; Cardiovascular disease; Administration schedule; Angina pectoris; Coronary heart disease; Long term
• ISSN: 0047-1828; 1347-4839
• DOI: 10.1253/jcj.47.1398

Molsidomine is a derivative of the sydnonimines and is a long-acting vasodilator that may be effective in the treatment of chronic stable angina pectoris. To evaluate the therapeutic efficacy and drug tolerance, eight men with stable angina pectoris performed a symptom-limited maximal exercise test on a computer-assisted treadmill. After ingesting either placebo or molsidomine administered treadmill. After ingesting either placebo or molsidomine administered in single blind fashion 90 min before the exercise test on the first day of treatment, molsidomine decreased the average systolic blood pressure response from 154 ± 3 (SEM) to 135 ± 4 mmHg (p < 0.01). However it did not significantly change the average heart rate response (117 ± 7 to 124 ± 8 beats/min) and the rate-pressure product (18.1 ± 1.2 × 103 to 16.8 ± 1.1 × 103). The average time up to the onset of ischemia at which significant ST-segment deviation (0.1 mV) first appeared was increased from 9.0 ± 1.7 to 12.8 ± 1.2 min (p < 0.001) after molsidomine. At peak exercise after molsidomine, the mean value of ST-segment deviation in V5 or aVF was decreased (p < 0.001). This result was obtained even though the average exercise duration was increased from 11.4 ± 1.7 to 13.6 ± 1.2 min (p < 0.001). The treadmill score according to Hollenberg was also improved from -47 ± 24 to 1 ± 14 after molsidomine administration. After six weeks of continued therapy with molsidomine the favorable effect on exercise tolerance was significantly decreased in terms of exercise duration, the time up to the onset of ischemia, and the treadmill score. The discontinuation of molsidomine treatment after six months' therapy did not deteriorate the exercise tolerance. Thus, molsidomine is effective in treating stable angina pectoris, but appears to possess a drug tolerance on long-term treatment.