Mono-amine transporters is a unique class of proteins that are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron. Thus, MATs are responsible for the uptake of monoamines by the sequential binding and co-transport of Na + and Cl ions. There are three major classes of MATs:dopamine (DAT), noradrenaline (NET), serotonin (SERT) that are responsible for the reuptake of their respective amine neurotransmitters e.g. dopamine, noradrenaline, and serotonin. MATs play an important role in neuronal signaling and several drugs targeting these proteins are used for treatment of depression e.g. tricyclic antidepressants and selective serotonin reuptake inhibitors, for treatment of attention deficit hyperactive disorder (ADHD) and narcolepsy e.g. methylphenidate and modafinil, and for neuropathic pain e.g. tricyclic antidepressants. Several factors determine the effect of drugs interacting with the MATs including the binding of the drug to the different MAT subtype, the binding within the transporter protein, and the concentrations of drug at each of the transporter subtypes in the intact organism.