The vesicular monoamine transporter (VMAT2) plays a major role in the synaptic accumulation and quantal release of monoamines. In this study, we assessed high affinity [(3)H]dihydrotetrabenazine binding to platelet VMAT2, in a group of untreated male Tourette's syndrome (TS) patients (age: 8-17.5 years, n=9) and in a group of age- and sex-matched healthy controls (age: 9-16 years, n=16). Significantly decreased platelet VMAT2 density (B(max)) (-23%, p=0.016) was observed in the TS patients. The affinity (K(d)) of the ligand to platelet VMAT2 was similar in both groups. If the lower platelet VMAT2 density also occurred in the brain, it may have serve as an adaptive mechanism geared to decrease dopamine storage in the presynaptic neurons and thereby to attenuate the dopaminergic overactivity and ameliorate the movement disorder.
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http://dx.doi.org/10.1016/j.euroneuro.2007.01.002 | DOI Listing |
Environ Toxicol Pharmacol
April 2024
Department of Biochemistry and Microbiology, Nelson Mandela University, Gqeberha, South Africa. Electronic address:
β-N-methylamino-l-alanine (BMAA) has been shown to inhibit vesicular monoamine transporter 2 (VMAT2), thereby preventing the uptake of monoaminergic neurotransmitters into platelet dense granules and synaptic vesicles. The inhibition is hypothesized to be through direct association of BMAA with hydroxyl groupꟷcontaining amino acid residues in VMAT2. This study evaluated whether BMAA-induced inhibition of VMAT2 could be prevented directly by co-incubation of BMAA with amino acids, and if this protection was specific for BMAA inhibition of VMAT2.
View Article and Find Full Text PDFToxicon
January 2023
Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth, 6021, South Africa. Electronic address:
The neurotoxic, non-proteinogenic amino acid β-N-methylamino-l-alanine (BMAA) has been implicated in the development of neurodegenerative diseases; however, the mechanism(s) and mode(s) of toxicity remain unclear. Similarities in the neuropathology and behavioural deficits of neonatal rats exposed to either BMAA or reserpine, a known vesicular monoamine transporter 2 (VMAT2) inhibitor, suggest a similar mode of action. The aims of this study were therefore to determine if BMAA could prevent the uptake of serotonin into dense granules via inhibition of VMAT2, and, if so, the type of inhibition caused by BMAA.
View Article and Find Full Text PDFBackground: Brain monoamine vesicular transport disease is an infantile onset neurodevelopmental disorder caused by variants in , which codes for the vesicular monoamine transporter 2 (VMAT2) protein, involved in the transport of monoamines into synaptic vesicles and of serotonin into platelet dense granules.
Case Presentation: The presented case is of a child, born of healthy consanguineous parents, who exhibited hypotonia, mental disability, epilepsy, uncontrolled movements, and gastrointestinal problems. A trial treatment with L-DOPA proved unsuccessful and the exact neurological involvement could not be discerned due to normal metabolic and brain magnetic resonance imaging results.
J Pharmacol Exp Ther
June 2017
Neurocrine Biosciences Inc., San Diego, California (D.E.G., E.S., H.B.); Pharmechanics, Wayne, Pennsylvania (S.R.J.H.); and Crinetics Pharmaceuticals, San Diego, California (A.M.).
The vesicular monoamine transporter 2 (VMAT2) is an integral presynaptic protein that regulates the packaging and subsequent release of dopamine and other monoamines from neuronal vesicles into the synapse. Valbenazine (NBI-98854), a novel compound that selectively inhibits VMAT2, is approved for the treatment of tardive dyskinesia. Valbenazine is converted to two significant circulating metabolites in vivo, namely, (+)--dihydrotetrabenazine (R,R,R-HTBZ) and a mono-oxy metabolite, NBI-136110.
View Article and Find Full Text PDFRev Neurol
March 2011
Servicio de Pediatría, Hospital Universitario Ramón y Cajal, Ctra. Colmenar Viejo, Madrid, Spain.
Introduction: A number of genetic and neuroimagen proofs support the idea that attention-deficit/hyperactivity disorder (ADHD) present a neurobiological alteration. Vesicular monoamine transporters (VMATs) are important proteins that regulate the intraneuronal monoamine concentration and disposition as this protein sequesters cytoplasmic dopamine within synaptic vesicles thus contributing to subsequent excitotoxic release.
Development: Two pharmacologically distinct VMAT isoforms VMAT1 and VMAT2 have been cloned and described.
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