Effect of antidepressant drugs on serotonergic and adrenergic receptors

Summary We examined eight tricyclic antidepressants (doxepin, amitriptyline, clomipramine, imipramine, trimipramine, nortriptyline, desipramine and protriptyline) and four nontricyclic antidepressants (mianserin, nomifensin, iprindole and zimelidine) in terms of their effects on serotonergic and adrenergic receptors by direct binding assays.³H-WB-4101 (0.22 nM) served as a label for postsynaptic alpha receptors while³H-clonidine (0.2 nM) served to label presynaptic alpha receptors in the frontal cortex of the calf.³H-dihydroalprenolol (³H-DHA) (0.5 nM) was used to label the beta₁ adrenoceptors in the calf frontal cortex and beta₂ adrenoceptors in the calf cerebellar cortex.³H-d-Lysergic acid diethylamide (³H-LSD) (2 nM) and³H-serotonin (³H-5HT) (0.5 nM) were used to label the serotonergic receptors in the calf frontal cortex.The results show that at drug concentrations which occur clinically in the plasma water, most of the tertiary amine tricyclics significantly inhibited³H-WB-4101,³H-LSD and³H-5HT binding. None of the antidepressants tested had any significant effect on³H-DHA binding. The secondary amine tricyclics as a group were not potent in inhibiting the binding of all four radiolabelled ligands. The nontricyclic antidepressant mianserin was potent in inhibiting the binding of³H-WB-4101,³H-clonidine,³H-LSD and³H-5HT. We suggest that the differences between the effects of the antidepressants on adrenergic and serotonergic receptors may be responsible for the differences in their therapeutic efficacies and side effects.Supported by the Canada Medical Research Council and the Ontario Mental Health FoundationA preliminary report of this work was presented at the 9th annual meeting of the Society for Neuroscience, Atlanta, 1979