Organic cation transporter 3 (OCT3)

Organic cation transporter 3 (OCT3) is a polyspecific, sodium-independent transporter encoded by the SLC22A3 gene, widely expressed in the heart, brain, liver, placenta, and other tissues. It mediates low-affinity, high-capacity uptake of a broad range of endogenous amines (such as dopamine, norepinephrine, serotonin, and histamine), xenobiotics, and many drugs. OCT3 plays a key role in the clearance of neurotransmitters—particularly in extraneuronal compartments—and is implicated in the regulation of mood, behavior, drug responses, and in the pharmacokinetics of several clinically important drugs such as metformin and tyrosine kinase inhibitors. Genetic polymorphisms in OCT3 affect its expression and function, thus influencing susceptibility to diseases including cardiovascular disease and cancer, and mediating variable drug efficacy and toxicity. Its inhibition by endogenous or pharmaceutical agents can lead to profound effects on neurotransmitter homeostasis and drug interactions.

Other names

Solute carrier family 22 member 3 (SLC22A3)Extraneuronal monoamine transporter (EMT)SLC22A3

Inhibition of OCT3 reduces clearance of monoamines, resulting in increased extracellular neurotransmitter concentrations (target for stress-induced relapse, relevant in neuropsychiatric disease and addiction); Drug substrates are transported via facilitated diffusion based on polyspecific recognition of cationic molecules; Some drugs act as competitive inhibitors, blocking transport of endogenous substrates and other drugs.