Antidepressants for the new millennium

Despite a remarkable structural diversity, most conventional antidepressant s may be viewed as 'monoamine based', increasing the synaptic availability of serotonin, norepinephrine, and/or dopamine. Both preclinical and recent clinical studies indicate that compounds which reduce transmission at N-met hyl-D-aspartate (NMDA) receptors are antidepressant. Moreover, chronic admi nistration of antidepressants to mice alters both the mRNA levels encoding N-methyl-D-aspartate receptor subunits and radioligand binding to these rec eptors within circumscribed areas of the central nervous system. It is hypo thesized that these two different treatment strategies converge to produce an identical functional endpoint: a region-specific dampening of NMDA recep tor function. The pathways leading to this convergence provide a rudimentar y framework for discovering novel antidepressants. (C) 1999 Elsevier Scienc e B.V. All rights reserved.