Effect of norepinephrine uptake blockers on norepinephrine kinetics

Abstract

The effect of a single oral dose of the neuronal norepinephrine [NE] uptake blocker desipramine 125 mg, a tricyclic antidepressant, on NE kinetics was studied. Desipramine reduced the plasma NE clearance by .apprx. 20%, from 1.33 .+-. 0.22 to 1.08 .+-. 0.19 l/m per min (P < 0.01). Plasma NE clearance was slowed in patients with sympathetic nerves damaged by disease (idiopathic peripheral autonomic insufficiency). Desipramine reduced the rate of spillover of NE to plasma, from 0.27 .+-. 0.07 to 0.15 .+-. 0.04 .mu.g/m2 per min, leaving the plasma NE concentration unchanged. Disappearance of [3H]-NE from plasma, after infusion to steady state, was biexponential, with half-time of the rapid-removal phase (t11/2) = 2.0 .+-. 0.4 min and half-time of the 2nd exponential (t21/2) = 34 .+-. 10 min. The rapid-removal phase was sensitive to disturbances in the neuronal uptake of NE, the t11/2 was prolonged by desipramine and lengthened in the patients with peripheral autonomic insufficiency. The selective extraneuronal NE uptake blocker, cortisol, 500 mg i.v., had no effect in normal subjects on plasma NE clearance or the t11/2 value. Neuronal uptake of NE contributes to the overall removal of NE from plasma. Extraneuronal uptake of NE could not be demonstrated at existing plasma NE concentrations.