Antagonism by antidepressants of serotonin S₁ and S₂ receptors of normal human brain in vitro

Using radioligand binding techniques and human frontal cortex, we determined the equilibrium dissociation constants (K_Ds) of 25 antidepressants at the serotonin S₁ (probably the S_1A subtype) and serotonin S₂ receptors using [³H]WB4101 and [³H]ketanserin, respectively. At the serotonin S₁ receptor, the most and least potent antidepressants were trazodone (K_D = 60 nM) and bupropion (K_D = 170 μM), respectively. At the serotonin S₂ receptor, the most and least potent antidepressants were amoxapine (K_D = 0.6 nM) and bupropion (K_D = 90 μM), respectively. Analysis of the data revealed a relationship between structure and serotonin S₁ affinity for some tricyclic antidepressants. Buspirone, a new anxiolytic agent, possessed high affinity for the serotonin S₁ receptor (K_D = 3.8 nM).