5-methoxytryptoline and close analogs as candidates for the endogenous ligand of the 3H-imipramine recognition site.

3H-Imipramine labels with high affinity a site associated with the macromolecular complex of the serotonin transporter in brain and platelets. There is a good correlation between the potencies of drugs at inhibiting 3H-5HT uptake and at inhibiting 3H-imipramine binding. Dissociation experiments indicate that the site labelled by 3H-imipramine is not identical with the substrate recognition site of the serotonin transporter and thus, it appears that 3H-imipramine labels a modulatory site for the 5HT transport system. On this basis, the existence of an endacoid acting on the 3H-imipramine recognition site to modulate 5HT uptake is discussed. The possibility that 5-methoxytryptoline or a closely related analog may be the endogenous ligand for the 3H-imipramine recognition site is analysed on the basis of the fact that 5-methoxytryptoline is a potent inhibitor of 3H-imipramine binding that also inhibits 3H-5HT uptake.