Toward a better understanding of depression and anxiety. The importance of tryptophan hydroxylase activation blockade: The origin of a unique anxiolytic antidepressant

Abstract

AbstractThe serotonin (5‐HT) deficiency theory of depression has misled medical science. Inhibitors of 5‐HT reuptake were the basis of the hypothesis and display limited efficacy with a pronounced delay of onset in action coupled with a side‐effect profile that includes increased anxiety. In the present commentary, a recommendation for the reinstatement of the prolongation of the d‐amphetamine stereotypy test is made as a means to generate new molecules capable of blocking stress‐induced tryptophan hydroxylase (TPH) activation and its elevation of 5‐HT, now regarded as the cause of depression The selective TPH activation inhibitor, AGN 2979, is already known to exert powerful, rapid antidepressant and anxiolytic properties in the clinic with a notable lack of the side effects associated with monoamine reuptake inhibition. Drug Dev Res 71:331–334, 2010. © 2010 Wiley‐Liss, Inc.