Association of [3H]-imipramine and [3H]-paroxetine binding with the 5HT transporter in brain and platelets: relevance to studies in depression.
[3H]-Imipramine and [3H]-paroxetine label with high affinity a site which is associated with the serotonergic transporter in brain and platelets. The pharmacological profile of inhibition by drugs of [3H]-imipramine and [3H]-paroxetine binding is highly correlated with the potency of the drugs to inhibit the uptake of 5HT. Denervation of serotonergic neurons by electrolytic lesions or with 5,7-dihydroxytryptamine produces marked decreases in the density of [3H]-imipramine as well as [3H]-paroxetine binding. Dissociation kinetic experiments support the view that the substrate recognition site for 5HT is different from the modulatory site which is labelled by [3H]-imipramine or [3H]-paroxetine. The existence of an endogenous ligand acting on the [3H]-imipramine recognition site to modulate the 5HT transporter was proposed by several laboratories. [3H]-Imipramine binding in platelets appears to be a biological marker in depression. Studies carried out in several laboratories report a significant decrease in the Bmax of platelet [3H]-imipramine binding without changes in Kd, when severely depressed untreated patients are compared with healthy volunteers matched for age and sex. The Bmax of platelet [3H]-imipramine binding appears to be a state-dependent biological marker in depression. It is tempting to speculate that the endocoid of the [3H]-imipramine recognition site may play a role in the pathogenesis of depression.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D001923:Brain Chemistry; D002352:Carrier Proteins; D003866:Depressive Disorder / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D006801:Humans; D007099:Imipramine / Q000378:metabolism*; D008297:Male; D017374:Paroxetine; D010880:Piperidines / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
D000928:Antidepressive Agents; D002352:Carrier Proteins; D010880:Piperidines; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; C027775:imipramine receptor; D012701:Serotonin; D017374:Paroxetine; D007099:Imipramine