Effects of nortriptyline and its 10-hydroxy metabolite on plasma noradrenaline (NA) concentrations, heart rate and blood pressure during intravenous NA infusion.

Eight healthy subjects were randomly given placebo and equimolar doses of nortriptyline (NT) and E-10-hydroxy-NT (E-10-OH-NT). Two hours after oral intake of drug, noradrenaline (NA) was infused intravenously at three consecutive rates. Before infusion of NA, E-10-OH-NT significantly increased heart rate compared to NT (p less than 0.05) and placebo (p less than 0.01). During NA infusion, the active drugs caused non-significant tendencies to augmented increase of blood pressure and decrease of heart rate. Plasma NA concentrations increased significantly due to the infused NA but were not influenced by NT or E-10-OH-NT. This absence of drug effect may have been due to several simultaneously operating factors affecting plasma NA concentrations, e.g., modification of the rates of NA release and clearance by exogenous NA or drugs and competing elimination pathways for infused NA. After stopping the NA infusion, a non-significant tendency to a slower elimination of NA was found after both active drugs.