TY  - JOUR
AU  - Rosenthal, Liana S
AU  - Farag, Mena
AU  - Aziz, N Ahmad
AU  - Bang, Jee
TI  - Vesicular monoamine transport inhibitors: current uses and future directions.
JO  - The lancet
VL  - 406
IS  - 10503
SN  - 0140-6736
CY  - London [u.a.]
PB  - Elsevier
M1  - DZNE-2025-00940
SP  - 650 - 664
PY  - 2025
AB  - Advancements over the past decade in understanding vesicular monoamine transporter 2 (VMAT2) inhibitors highlight their key role in the treatment of movement and neuropsychiatric disorders. VMAT2 is crucial for packaging neurotransmitters such as serotonin, dopamine, and norepinephrine into synaptic vesicles, facilitating their release and reuptake in synaptic transmission. VMAT2 inhibitors, such as tetrabenazine, deutetrabenazine, and valbenazine, show therapeutic efficacy in managing hyperkinetic movement disorders, including Huntington's disease, tardive dyskinesia, and Tourette's syndrome. These inhibitors modulate excessive synaptic activity by reducing neurotransmitter storage and release. Genetic variations, particularly in the cytochrome P450 enzyme family, influence VMAT2 inhibitor metabolism, necessitating personalised dosing to optimise efficacy and minimise adverse events. Recent studies have provided further structural insights into VMAT2 inhibition mechanisms, paving the way for the development of inhibitors with enhanced potency and selectivity. Leveraging pharmacogenetics for precision medicine and exploring VMAT2 inhibition in broader therapeutic contexts could revolutionise treatment frameworks for neurological and psychiatric conditions.
KW  - Humans
KW  - Vesicular Monoamine Transport Proteins: antagonists & inhibitors
KW  - Vesicular Monoamine Transport Proteins: metabolism
KW  - Tetrabenazine: analogs & derivatives
KW  - Tetrabenazine: therapeutic use
KW  - Tetrabenazine: pharmacology
KW  - Huntington Disease: drug therapy
KW  - Movement Disorders: drug therapy
KW  - Valine: analogs & derivatives
KW  - Vesicular Monoamine Transport Proteins (NLM Chemicals)
KW  - Tetrabenazine (NLM Chemicals)
KW  - SLC18A2 protein, human (NLM Chemicals)
KW  - deutetrabenazine (NLM Chemicals)
KW  - valbenazine (NLM Chemicals)
KW  - Valine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40783291
DO  - DOI:10.1016/S0140-6736(25)01072-4
UR  - https://pub.dzne.de/record/280285
ER  -