[3H]tetrahydrotrazodone binding. Association with serotonin binding sites.

High (17 nM) and low (603 nM) affinity binding sites for [3H]tetrahydrotrazodone ([3H] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes. The substrate specificity, concentration, and subcellular and regional distributions of these sites suggest that they may represent a component of the serotonin transmitter system. Pharmacological analysis of [3H]THT binding, coupled with brain lesion and drug treatment experiments, revealed that, unlike other antidepressants, [3H] THT does not attach to either a biogenic amine transporter or serotonin binding sites. Rather, it would appear that [3H]THT may be an antagonist ligand for the serotonin binding site. This probe may prove of value in defining the mechanism of action of trazodone and in further characterizing serotonin receptors.