Figure 1.

The experimental protocol. After preparation and stabilization, infusion of phenylephrine at 75 nmol kg⁻¹ min⁻¹ was started at time 0 min. At 5 min the first dose of the drug of interest was given, either as a bolus dose (e.g. halofantrine) or as a continuous infusion (e.g. clofilium or terfenadine). At 15 min the infusion rate for phenylephrine was increased to 150 nmol kg⁻¹ min⁻¹ with further increases to 225 and 300 nmol kg⁻¹ min⁻¹ at 18 and 21 min. Both infusions were switched off at 24 min and a 10 min drug-free interval allowed. This cycle of drug administration was repeated twice more using the same infusion rates for phenylephrine but increasing the dose of the drug of interest by approximately 3 fold each time.