Kinetic effects of desmethylimipramine treatment on platelet serotonin uptake in depressed patients: a comparison with imipramine.
The kinetic effects of desmethylimipramine (DMI) on platelet serotonin (5HT) uptake were compared to those of imipramine (IMI) in eight DMI-treated depressed patients and seven IMI-treated depressed patients, and compared to values after patients were off drug for 19 (+/- 8 SD) and 33 (+/- 15) days. As expected, IMI was a stronger inhibitor of 5HT uptake than DMI during treatment, with the mean apparent Km in treated patients being elevated nearly threefold over that of the drug-free condition. In DMI-treated patients, the mean Km was elevated nearly twofold over that of the drug-free condition. Although DMI is considered a preferential norepinephrine uptake inhibitor, the results suggest the following: (1) Significant decreases in the apparent platelet 5HT affinity are achieved with DMI; (2) the inhibition kinetics in depressed patients are competitive; (3) there was a significant relationship between Km change and depression outcome with DMI discontinuation; and (4) DMI, as a metabolite, appears to contribute to the 5HT uptake inhibition of IMI in vivo.
Rausch
J L
JL
Department of Psychiatry, San Diego, Department of Veterans Affairs Medical Center, La Jolla, CA.
Moeller
F G
FG
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D003891:Desipramine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007099:Imipramine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000097:blood*
D011985:Receptors, Serotonin; D012701:Serotonin; D007099:Imipramine; D003891:Desipramine