A comparison of the β1–selectivity of conventional metoprolol and metoprolol CR during exercise in healthy volunteers

SUMMARY This paper reports on a randomized double–blind crossover study to compare the effects of daily treatment with 100 mg conventional metoprolol (M100), 50 or 100 mg slow–release metoprolol CR (CR50, CR100) and placebo on the response to treadmill walking exercise in 12 healthy volunteers. Twenty minutes of exercise was undertaken at 15 h post–dose (Exl) and again at 4 h (Ex2). During Exl all metoprolol preparations caused a reduction in the exercise–induced increase in heart rate when compared to placebo (P <0001). 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 < 005). Rises in plasma ammonia were used to assess the net degradation of energy–rich adenine nucleotides by skeletal muscle during exercise. When compared to placebo, a significant elevation in plasma ammonia was seen only during exercise with M100 (P < 005). The perceived exertion at the end of exercise was also greatest on conventional metoprolol. The differences between the effects of conventional and CR formulations of metoprolol were less when exercise was repeated 4 h post dosing. We conclude that metoprolol CR may offer advantages over the conventional preparation, in subjects regularly engaging in exercise, by reducing the metabolic stress imposed upon skeletal muscle.