MRAs cause the release of<unk>  neurotransmitters by various complex mechanism of actions. They may enter the presynaptic neuron primarily via plasma membrane transporters, such as the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT). Some, such as exogenous phenethylamine, amphetamine, and methamphetamine, can also diffuse directly across the cell membrane to varying degrees. Once inside the presynaptic neuron, they may inhibit the reuptake of<unk>  neurotransmitters through vesicular<unk>  transporter 2 (VMAT2) and release the neurotransmitters stores of synaptic vesicles into the cytoplasm by inducing reverse transport at VMAT2. MRAs can also bind to the intracellular receptor TAAR1 as agonists, which triggers a phosphorylation cascade via protein kinases that results in the phosphorylation of<unk>  transporters located at the plasma membrane (i.e., the dopamine transporter, norepinephrine transporter, and serotonin transporter); upon phosphorylation, these transporters transport<unk> s in reverse (i.e., they move<unk> s from the neuronal cytoplasm into the synaptic cleft). The combined effects of MRAs at VMAT2 and TAAR1 result in the release of neurotransmitters out of synaptic vesicles and the cell cytoplasm into the synaptic cleft where they bind to their associated presynaptic autoreceptors and postsynaptic receptors. Certain MRAs interact with other presynaptic intracellular receptors which promote<unk>  neurotransmission as well (e.g., methamphetamine is also an agonist at σ1 receptor).
Monoamine releasing agent
Dopamine releasing agent
Serotonin releasing agent
Monoamine-depleting agent
Serotonin–norepinephrine releasing agent
Chaotropic agent
Norepinephrine releasing agent
Norepinephrine–dopamine releasing agent