Sumatriptan reduces exercise capacity in healthy males: a peripheral effect of 5-hydroxytryptamine agonism?

5-Hydroxytryptamine (5-HT; serotonin) has been implicated in the perception of exercise-induced fatigue. Sumatriptan is a selective 5-HT1B/D receptor agonist which does not cross the blood-brain barrier. The aim of the presen t study was to determine the effect of sumatriptan on exercise capacity. Te n healthy male subjects (mean age 28.4 +/- 10.8 years) performed a maximal treadmill exercise test according to the Bruce protocol with expired gas an alysis on two occasions. Either 6 mg of sumatriptan or placebo was administ ered subcutaneously in a randomized, double-blind, placebo-controlled, cros s-over design. Exercise time was greater after placebo compared with sumatr iptan [914 and 879 s respectively; 95% confidence interval (CI) of differen ce 12.1 s, 59.1 s; P = 0.008]. There was no significant effect on peak oxyg en consumption (placebo, 50.6 +/- 6.3 ml.min(-1).kg(-1); sumatriptan, 51.7 +/- 7.6 ml.min(-1).kg(-1)). Sumatriptan administration resulted in decrease s in both heart rate(sumatriptan, 188 +/- 14 beats/min, placebo, 196 +/- 12 beats/min; 95% CI of difference 12.6, 2.6; P = 0.008) and respiratory exch ange ratio (sumatriptan, 1.23 +/- 0.06; placebo, 1.26 +/- 0.07; 95% CI of d ifference 0.05, 0.01; P = 0.01) at peak exercise. There were no significant differences in blood pressure, heart rate or submaximal oxygen consumption between sumatriptan and placebo treatments at any stage of exercise. Thus sumatriptan reduces maximal exercise capacity in normal males. The failure to demonstrate any haemodynamic or cardiorespiratory effect suggests that s umatriptan enhances perception of fatigue by a peripheral mechanism affecti ng 5-HT modulation.