Serotonin transporters: Implications for antidepressant drug development

Natural and engineered coding variation in antidepressant-sensitive serotonin transporters.

The presynaptic serotonin (5-HT) transporter (SERT) is a key regulator of 5-HT signaling and is a major target for antidepressant medications and psychostimulants. In recent years, studies of natural and engineered genetic variation in SERT have provided new opportunities to understand structural dimensions of drug interactions and regulation of the transporter, to explore 5-HT contributions to...

Phosphorylation and regulation of antidepressant-sensitive serotonin transporters.

Antidepressant-sensitive serotonin (5-hydroxytryptamine, 5HT) transporters (SERTs) are responsible for efficient synaptic clearance of extracellular 5HT. Previously (Qian, Y., Galli, A., Ramamoorthy, S., Risso, S., DeFelice, L. J., and Blakely, R. D. (1997) J. Neurosci. 17, 45-47), we demonstrated that protein kinase (PKC)-linked pathways in transfected HEK-293 cells lead to the internalization...

Autoregulation of serotonin neurons: role in antidepressant drug action.

Antidepressant Tolerability and Potential Clinical Implications of Serotonin-2A Genotypes

Since the introduction of monoamine oxidase inhibitors (MAOIs) in the 1950s, researchers have been searching for antidepressant agents with more favorable tolerability profiles. The introduction of selective serotonin reuptake inhibitors (SSRIs) in the late 1980s provided clinicians with a drug class featuring an improved tolerability profile as compared to MAOIs and tricyclic antidepressants (...

Drug transporters and imatinib treatment: implications for clinical practice.

Imatinib mesylate is approved for the treatment of chronic myeloid leukemia (CML) and advanced gastrointestinal stromal tumors (GIST). Unfortunately, in the course of treatment, disease progression occurs in the majority of patients with GIST. Lowered plasma trough levels of imatinib over time potentially cause disease progression, a phenomenon known as "acquired pharmacokinetic drug resistance...