On the mode of action of imipramine: relationship between serotonergic axon terminal function and down-regulation of beta-adrenergic receptors

Recognition sites for [3H]imipramine and [3H]mianserin are located in different structures and regulate different neuronal functions. Recognition sites for [3H]imipramine are located on serotonergic terminals, are part of the supramolecular organization of the uptake mechanisms and can be down-regulated by prolonged administration of the drug. When the number of recognition sites for imipramine is down-regulated, uptake of 5-hydroxytryptamine (5HT) in rat brain hippocampal slices is increased. The presence of the binding sites for imipramine in 5HT terminals is essential to mediate the down-regulation of recognition sites for norepinephrine (NE) and NE-mediated stimulation of adenylate cyclase. Mianserin binds on a site that is modulated by 5HT, the number of its binding sites is not down-regulated by repeated treatment and, like imipramine, decreases the NE-dependent cyclase but not the number of beta-adrenergic receptor recognition sites. Repeated treatment with imipramine and mianserin down-regulated the number of 5HT2 recognition sites. Several lines of evidence indicate that binding site for mianserin is related but not identical to the 5HT2 receptor binding site.