High-Affinity Binding of Antidepressants to Platelets and Brain Tissues
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Although antidepreβant drug treatment is a well-established therapeutic approach in manic-depreβive disorders, the mechanism by which such drugs ameliorate the depreβive syndromes remains an area of active research. The mechanism of action of antidepreβants most likely has two components. The clinical manifestation of their therapeutic effects generally is seen after a l-to 2-wk treatment, thus implying that a degree of neuronal adaptation under the effect of antidepreβants is required for clinical efficacy. The development of neuronal sub-or supersensitivity following subchronic antidepreβant treatment, however, is thought to be secondary to the direct interaction of these drugs with specific receptors and/or enzymes in the brain. To characterize this interaction of antidepreβants with such receptors and/or enzymes, radioligand binding studies using mostly 3 H-labeled antidepreβants have been used extensively. Foremost among these is [3 H]-imipramine, a tricyclic antidepreβant that inhibits neuronal serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (noradrenaline, NA) transport. Other radiolabeled antidepreβants whose high-affinity binding sites have been studied in the brain and peripheral tiβues include [3 H]-desipramine, [3 H]-nomifensine, [3 H]-indalpine, [3 H]-paroxetine, [3 H]-cyanoimipramine, [3 H]-amitriptyline, [3 H]-doxepin, [3 H]-mianserin, and [3 H]-rolipram (Table 1
