Vesicular Monoamine Transporters at the Crossroads of Structure and Function: Advances, Challenges, and Future Perspectives.

Authors

Kai H Lange, Michael P Dalton, Suraj Kumar Mandal, Jonathan A Coleman

Published in

Annual review of pharmacology and toxicology. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

Monoaminergic signaling controls many aspects of human physiology, including autonomic responses, movement, and emotion. The vesicular monoamine transporters (VMAT1 and VMAT2) sequester monoamines into synaptic vesicles within the central and peripheral nervous system. Dysregulation of VMAT function contributes to neuropsychiatric and neurodegenerative disorders, including Parkinson's disease, depression, and psychostimulant substance abuse. Clinically, VMATs are targeted by the inhibitors tetrabenazine and reserpine, used to treat hyperkinetic movement disorders and hypertension, respectively, while amphetamines exploit VMAT2-mediated dopamine efflux to treat ADHD. Emerging VMAT2-selective compounds such as lobeline derivatives and GZ-11610 attenuate psychostimulant reinforcement. Tricyclic antidepressants upregulate VMAT2 function and rescue disease-causing variants, highlighting VMAT2 as a promising therapeutic target. Despite their importance, the molecular mechanisms driving proton-coupled transport, inhibition, and psychostimulant action remain poorly understood. This review summarizes current biochemical, structural, and functional insights into VMATs, highlighting proton coupling, transport kinetics, inhibition mechanisms, unresolved questions, and future research directions.

PMID:
42566692
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.