Current perspectives on the development of non-biogenic amine-based antidepressants.

Compounds that inhibit the re-uptake and/or metabolism of biogenic amines (i.e. serotonin, norepinephrine, and dopamine) have been used to treat depression for more than 40 years. Selective re-uptake inhibitors, currently the most widely prescribed class of biogenic amine-based agents, are certainly safe and relatively easy to use, but do not exhibit either a faster onset of action or greater efficacy than their predecessors. An approach to overcome the limitations that may be inherent to these 'conventional' therapies is to circumvent the monoaminergic synapse. In this review, two potential antidepressant strategies are discussed that may converge with intracellular pathways impacted by chronic treatment with biogenic amine-based agents. Drugs emerging from these strategies may offer significant advantages over currently used antidepressants. Copyright 2001 Academic Press.