Modulating monoamine activity as a therapeutic strategy continues to domina
te antidepressant research, with a recent emphasis on agents with multiple
targets, including combined serotonin/noradrenaline re-uptake inhibitors an
d numerous serotonin receptor ligands. An important new development has bee
n the emergence of potential novel mechanisms of action, notably modulation
of the activity of neuropeptides substance P and corticotrophin-releasing
factor, and the intracellular messenger cyclic adenosine monophosphate. Eff
orts in this area have recently been rewarded by the demonstration of antid
epressant efficacy of the substance P receptor antagonist MK-0869.