Monoamine transporters: vulnerable and vital doorkeepers

Abstract

Transporters of dopamine, serotonin, and norepinephrine have been empirically used as medication targets for several mental illnesses in the last decades. These protein-targeted medications are effective only for subpopulations of patients with transporter-related brain disorders. Since the cDNA clonings in early 1990s, molecular studies of these transporters have revealed a wealth of information about the transporters' structure-activity relationship (SAR), neuropharmacology, cell biology, biochemistry, pharmacogenetics, and the diseases related to the human genes encoding these transporters among related regulators. Such new information creates a unique opportunity to develop transporter-specific medications based on SAR, mRNA, DNA, and perhaps transporter trafficking regulation for a number of highly relevant diseases including substance abuse, depression, schizophrenia, and Parkinson's disease.

Figure 1. Schematic of clinical relevance of monoamine transporters (MATs in blue) or vesicular monoamine transporters (VMATs in brown): regulation (black arrow) of activity and expression by small molecules, proteins and DNA sequence polymorphisms ( see “x”)

Clinical roles of MAT inhibitors are indicated on the left hand side and diseases contributed by genetic variations lisyed on the right side. Green dot, monoamine. Horizontal arrow, MAT gene.