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 (KDs) of 25 antidepressants at the serotonin S1 (probably the S1A 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 (KD = 60 nM) and bupropion (KD = 170 microM), respectively. At the serotonin S2 receptor, the most and least potent antidepressants were amoxapine (KD = 0.6 nM) and bupropion (KD = 90 microM), 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 (KD = 3.8 nM).