PMID: 11606618Oct 19, 2001Paper

Physiological genomics of antidepressant targets: keeping the periphery in mind

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
R D Blakely

Abstract

The plasma membrane transporters that clear extracellular serotonin (5-HT) and norepinephrine (NE), serotonin transporters (SERTs) and NE transporters (NETs), have received considerable attention over the past four decades because of their roles in amine neurotransmitter inactivation. In addition, they interact with many centrally active drugs, including multiple classes of antidepressants such as the serotonin-selective reuptake inhibitors, typified by fluoxetine (Prozac), and the more recently developed norepinephrine-selective transporter antagonists, such as reboxetine. The therapeutic utility of these agents supports biogenic amine theories of affective disorders and raises the question as to whether SERT and NET exhibit a functional genetic variation that could influence risk for behavioral disorders. Although evidence exists that a promoter polymorphism in SERT may influence behavioral states, this contention is not without complexity and its mechanism of action remains poorly understood. The identification of coding variants of NETs and SERTs would offer important opportunities to connect genotype to phenotype. However, given the limited frequency of transporter coding variations evident to date in general population su...Continue Reading

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