A COMPARISON OF THE BETA(1)-SELECTIVITY OF CONVENTIONAL METOPROLOL AND METOPROLOL CR DURING EXERCISE IN HEALTHY-VOLUNTEERS

This paper reports on a randomized double-blind crossover study to com pare the effects of daily treatment with 100 mg conventional metoprolo l (M100), 50 or 100 mg slow-release metoprolol CR (CR50, CR100) and pl acebo on the response to treadmill walking exercise in 12 healthy volu nteers. Twenty minutes of exercise was undertaken at 1.5 h post-dose ( Ex1) and again at 4 h (Ex2). During Ex1 all metoprolol preparations ca used a reduction in the exercise-induced increase in heart rate when c ompared to placebo (P<0.001). The exercise-induced increase in plasma glycerol, an indicator of lipolysis, was diminished by all metoprolol preparations but to a greater extent by M100 (P<0.05). Rises in plasma ammonia were used to assess the net degradation of energy-rich adenin e nucleotides by skeletal muscle during exercise. When compared to pla cebo, a significant elevation in plasma ammonia was seen only during e xercise with M100 (P<0.05). The perceived exertion at the end of exerc ise was also greatest on conventional metoprolol. The differences betw een the effects of conventional and CR formulations of metoprolol were less when exercise was repeated 4 h post dosing. We conclude that met oprolol CR may offer advantages over the conventional preparation, in subjects regularly engaging in exercise, by reducing the metabolic str ess imposed upon skeletal muscle.