Desipramine binding to noradrenaline reuptake sites in cardiac sympathetic neurons 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 [11C]meta-hydroxyephedrine and the multiple organs' coincidences counter. Eight healthy volunteers had two scans, one with tracer alone and one after preloading with desipramine 50-75 mg p.o. In all subjects, there was an increased 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 [11C]meta-hydroxyephedrine time activity curve (t=7. 4; P=0.001). In one subject who had three doses of desipramine, the increase in washout rate was dose-dependent. In conclusion, [11C]meta-hydroxyephedrine in the multiple organs' coincidences counter gives a valid, low radiation method to assess noradrenergic reuptake blockade in the clinic.
Malizia
A L
AL
Psychopharmacology Unit, University of Bristol, Bristol, UK. andrea.l.malizia@bristol.ac.uk
Melichar
J K
JK
Rhodes
C G
CG
Haida
A
A
Reynolds
A H
AH
Jones
T
T
Nutt
D J
DJ
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001665:Binding Sites; D002250:Carbon Radioisotopes; D003287:Contrast Media; D003891:Desipramine / Q000494:pharmacology; D004809:Ephedrine / Q000031:analogs & derivatives; D005720:Gamma Rays; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation*; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011877:Radionuclide Imaging; D013564:Sympathetic Nervous System / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism*
D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D002250:Carbon Radioisotopes; D003287:Contrast Media; C065363:3-hydroxyephedrine; D004809:Ephedrine; D003891:Desipramine; D009638:Norepinephrine