Allosteric modulation of monoamine transporters – new drug targets in depression

Current antidepressants modulate monoaminergic neurotransmission via interaction with receptors, transporters and/or metabolism. Drug discovery programs focus mostly on orthosteric drugs that compete with the endogenous ligand for its primary binding site. There is growing interest in allosteric modulators that act via nonorthosteric binding sites. Allosteric modulation of the serotonin transporter is likely to contribute to the therapeutic effect of the selective 5-HT reuptake inhibitor, escitalopram. Therapeutic perspectives of allosteric modulation of monoamine transporters are discussed.

Section editors:David Sibley – National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, USAC. Anthony Altar – Psychiatric Genomics, Gaithersburg, USATheresa Branchek – Lundbeck Research, Paramus, USA