In this review we will focus on five prototypic stimulant drugs that have been studied most intensively: amphetamine, methamphetamine, methylphenidate, cocaine, and bupropion. All of these drugs inhibit the reuptake of dopamine, norepinephrine, and serotonin, thereby increasing the levels of these monoamine neurotransmitters in the synaptic cleft. These drugs differ in their potency, synaptic actions, degree of reuptake blockade, pharmacokinetic properties and their specificity and actions on other neurotransmitter systems. Some of the drugs (e.g., amphetamine) also cause the reuptake transporters to work in reverse, leading to non-impulse dependent release of neurotransmitters. Additionally, some stimulants inhibit the monoamine oxidase enzymes (MAO-A and MAO-B), thus preventing the degradation of monoamines (Seiden et al. 1993). Finally, there is evidence that stimulant drugs disrupt the function of the vesicular monoamine transporter type 2 (VMAT2), which transports monoamine neurotransmitters from stores in the cytoplasm to synaptic vesicles (Uhl et al. 2000). Genetic variation in these genes as well as in their up- or down-stream neighbors make them likely candidates to contribute to inter-individual variation in the response to stimulant drugs.
