The vesicular monoamine transporters, VMAT1 and VMAT2, play crucial roles in packing neurotransmitters into synaptic vesicles, essential for neurotransmission and protecting cells from toxic cytosolic monoamines. While VMAT1 is primarily found in neuroendocrine cells, VMAT2 is predominant in the central nervous system and is implicated in various neurological and psychiatric disorders, including Parkinson’s disease and schizophrenia. VMAT2’s function in dopaminergic neurons is particularly significant, as it helps prevent oxidative stress by sequestering dopamine into vesicles, thereby reducing the production of harmful reactive oxygen species.

Recent research has identified several FDA-approved drugs that inhibit VMAT2, including some that were not previously associated with this function, such as salmeterol (a β2-adrenergic receptor agonist) and ziprasidone (an atypical antipsychotic). These findings, validated through various biochemical and computational methods, suggest potential new therapeutic avenues for conditions like tardive dyskinesia and Huntington’s disease. The study also emphasizes the need for further exploration of VMAT2’s role in drug action, both for repurposing existing medications and for understanding off-target effects.

Reference: Støve SI, Skjevik ÅA, Teigen K, Martinez A. Inhibition of VMAT2 by β2-adrenergic agonists, antagonists, and the atypical antipsychotic ziprasidone. Commun Biol. 2022;5(1):1283. doi: 10.1038/s42003-022-04121-1.