Objective evaluation of PY-108-068, a new calcium channel inhibitor for the treatment of chronic stable angina pectoris.
PY-108-068 (PY) has calcium antagonist and coronary dilatory activity in animals, suggesting that it may be useful for the treatment of angina pectoris. We have studied its effects in 19 patients with stable exertional angina. After a 2-week single-blind placebo run-in phase, patients were randomised double-blind to either 75 mg or 150 mg of the drug (in three divided doses) daily for 2 weeks, crossing over to the alternate dose for a further 2 weeks. Maximal treadmill tests with computer-assisted electrocardiographic analysis were used to evaluate efficacy. The mean +/- SEM exercise time to onset of angina increased from 6.1 +/- 0.5 min on placebo to 9.3 +/- 0.8 min on PY 75 mg (P less than 0.001) and to 9.2 +/- 0.8 min on PY 150 mg (P less than 0.001) vs placebo; NS vs 75 mg). The time to development of 1 mm ST-segment depression in lead CC5 also increased from 5.0 +/- 0.7 min on placebo to 6.4 +/- 0.9 min on PY 75 mg (P less than 0.01) and to 7.0 +/- 0.8 min on PY 150 mg (P less than 0.01 vs placebo; NS vs 75 mg). Unlike other calcium antagonists, treatment with PY-108-068 did not significantly alter the resting or maximal heart rates or the heart rate gain during exercise. Resting blood pressure was reduced at the higher dose level but peak blood pressure during exercise and peak double product were unaltered by PY-108-068 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005080:Exercise Test; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D009543:Nifedipine; C034600:darodipine