FIG. 1

The evolution of antidepressant pharmacotherapy from classes discovered by chance observation, (tricyclic antidepressants [TCAs] and monoamine oxidase inhibitors [MAOIs]) to those that were rationally designed to have specific mechanism(s) of action while avoiding other effects. NE, norepinephrine; SE, serotonin; DA, dopamine; Ach, acetylcholine receptor antagonism; SSRI, selective serotonin reuptake inhibitor (fluoxetine, sertraline, paroxetine, fluvoxamine); * at clinically relevant plasma concentrations nefazodone acts both as a serotonin-2A receptor antagonist and a serotonin reuptake inhibitor; ** receptor affects presumed to mediate antidepressant efficacy include serotonin-2A receptor antagonism (trazodone, nefazodone, mirtazapine) and presynaptic alpha-2 adrenergic receptor antagonism (mirtazapine)

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published 2000