Schematic representation of the design of studies 1 and 2. The blue line is the infusion rate of alfentanil. In study 1, the infusion could be adapted depending on magnitude of the ventilatory (a doubling of loading and maintenance dose in case the target of respiratory depression, 25–30%, was not attained; a reduction of the maintenance dose by 50% in case of an overshoot in respiratory depression). The red line is the infusion rate of GAL021 or placebo. In study 1, respiration was measured under isohypercapnic conditions; in study 2 poikilocapnic ventilatory and nonventilatory variables were obtained. B represents baseline (no drug, no added inspired carbon dioxide), C represents the carbon dioxide clamp before any drug infusion, P1 represents low-dose alfentanil (ALF) infusion before GAL021 or placebo infusion (ALF-low), P2 the combination of low-dose alfentanil and low-dose GAL021 or placebo (ALF-low plus GAL021-low), P3 the combination of low-dose alfentanil with high-dose GAL021 or placebo (ALF-low plus GAL021-high), and P4 the combination of high-dose alfentanil with high-dose GAL021 or placebo (ALF-high plus GAL021-high). Alfentanil and GAL021 infusion rate are in μg kg⁻¹ h⁻¹.