Desipramine binding to noradrenaline reuptake sites in cardiac sympatheticneurons in man in vivo

Noradrenergic reuptake blockade is a recognised mechanism of antidepressant action, but the extent of the blockade necessary for therapeutic effect is not known and plasma levels do not provide a guide to therapy. We report a method to assess noradrenaline reuptake blockade in vivo in man using [C-1 1]meta-hydroxyephedrine and the multiple organs' coincidences counter. Eigh t healthy volunteers had two scans, one with tracer alone and one after pre loading with desipramine 50-75 mg p.o. In all subjects, there was an increa sed washout rate of the radioligand from the heart following preloading (t = 4.38; P < 0.003) as well as a decrease of the area under the [C-11]meta-h ydroxyephedrine time activity curve (t = 7.4; P = 0.001). In one subject wh o had three doses of desipramine, the increase in washout rate was dose-dep endent. In conclusion, [C-11]meta-hydroxyephedrine in the multiple organs c oincidences counter gives a valid, low radiation method to assess noradrene rgic reuptake blockade in the clinic. (C) 2000 Elsevier Science B.V. All ri ghts reserved.