The antiserotonin agent pizotifen does not increase endurance performance in humans.

This study investigated the effect of the serotonin receptor antagonist pizotifen on endurance performance during treadmill exercise in humans. Eight healthy men exercised to exhaustion on a treadmill at an intensity corresponding to 70% of their maximal oxygen uptake (VO2max). Pizotifen was administered orally in a 1-mg dose 5 h before the start of exercise. The study was double blind, using a randomized, placebo-controlled crossover design. Oxygen uptake, heart rate, and ratings of perceived exertion were measured and blood samples taken for determination of concentrations of lactate, glucose, amino acids, ammonia, and haematocrit. Measurements were made at intervals of 30 min during the run and at exhaustion. There was no significant difference between the placebo and the pizotifen trials for any of the variables except for the plasma free-tryptophane: branched chain amino acid ratio which was somewhat lower after pizotifen at postexercise. Pizotifen did not increase exercise time to exhaustion, which was even shorter after pizotifen than after placebo in seven out of the eight subjects; the difference between pizotifen and placebo did not reach the level of statistical significance [109.4 (SD 6.7) min after pizotifen versus 119.8 (SD 12.5) min after placebo]. The results do not support the hypothesis that there is a central component to fatigue which is mediated by the serotoninergic neurones.