Article

Tetrabenazine in the treatment of hyperkinetic movement disorders

Department of Neurology, Parkinson's disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, TX, USA.
Expert Review of Neurotherapeutics (Impact Factor: 2.78). 02/2006; 6(1):7-17. DOI: 10.1586/14737175.6.1.7
Source: PubMed

ABSTRACT

Tetrabenazine, a dopamine-depleting agent first synthesized half a century ago, was initially developed for the treatment of schizophrenia. Although psychotic disorders have since been treated more successfully with other neuroleptic medications, many studies have shown this drug to be effective in the treatment of hyperkinetic movement disorders (hyperkinesias). Hyperkinesias are neurologic disorders characterized by abnormal involuntary movements such as chorea associated with Huntington's disease, tics in Tourette's syndrome and stereotypies in tardive dyskinesia. Recently, clinical trials investigating tetrabenazine for the treatment of chorea associated with Huntington's disease found the drug to be safe and efficacious, making approval by the US Food and Drug Administration for this indication a distinct possibility.

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    • "TD may be a potentially irreversible condition with most treatment modalities having less satisfactory outcome which may require complex dosing , have their own adverse effects and use for long periods that may not be desirable [Lerner et al. 2015; Waln and Jankovic, 2013]. Various treatments have been used including the use of clozapine and quietiapine [Emsley et al. 2004], dopamine-depleting agents like tetrabenazine and amantaidine [Aia et al. 2011; Kenney and Jankovi, 2006], gamma amino butyric acid (GABA) agonists like valproate and clonazepam [Aia et al. 2011; Aladed et al. 2011] and anticholinergic medications such as trihexyphenidyl [Fernandez and Friedman, 2003]. Less commonly studied agents which might be effective include pyridoxine [Waln and Jankovic, 2013]. "

    Full-text · Article · Dec 2015 · Therapeutic Advances in Psychopharmacology
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    • "TD may be a potentially irreversible condition with most treatment modalities having less satisfactory outcome which may require complex dosing , have their own adverse effects and use for long periods that may not be desirable [Lerner et al. 2015; Waln and Jankovic, 2013]. Various treatments have been used including the use of clozapine and quietiapine [Emsley et al. 2004], dopamine-depleting agents like tetrabenazine and amantaidine [Aia et al. 2011; Kenney and Jankovi, 2006], gamma amino butyric acid (GABA) agonists like valproate and clonazepam [Aia et al. 2011; Aladed et al. 2011] and anticholinergic medications such as trihexyphenidyl [Fernandez and Friedman, 2003]. Less commonly studied agents which might be effective include pyridoxine [Waln and Jankovic, 2013]. "

    Full-text · Article · Dec 2015 · Therapeutic Advances in Psychopharmacology
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    • "Lastly, our observations must be interpreted carefully. TBZ has been used to treat movement disorders for over 30 years (Kenney & Jankovic 2006) and effects on glucose homeostasis have not been reported. Nevertheless, our findings suggest that VMAT2 plays a role in glucose homeostasis and could be a therapeutic target in diabetes. "
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    ABSTRACT: Despite different embryological origins, islet beta-cells and neurons share the expression of many genes and display multiple functional similarities. One shared gene product, vesicular monoamine transporter type 2 (VMAT2, also known as SLC18A2), is highly expressed in human beta-cells relative to other cells in the endocrine and exocrine pancreas. Recent reports suggest that the monoamine dopamine is an important paracrine and/or autocrine regulator of insulin release by beta-cells. Given the important role of VMAT2 in the economy of monoamines such as dopamine, we investigated the possible role of VMAT2 in insulin secretion and glucose metabolism. Using a VMAT2-specific antagonist, tetrabenazine (TBZ), we studied glucose homeostasis, insulin secretion both in vivo and ex vivo in cultures of purified rodent islets. During intraperitoneal glucose tolerance tests, control rats showed increased serum insulin concentrations and smaller glucose excursions relative to controls after a single intravenous dose of TBZ. One hour following TBZ administration we observed a significant depletion of total pancreas dopamine. Correspondingly, exogenous L-3,4-dihydroxyphenylalanine reversed the effects of TBZ on glucose clearance in vivo. In in vitro studies of rat islets, a significantly enhanced glucose-dependent insulin secretion was observed in the presence of dihydrotetrabenazine, the active metabolite of TBZ. Together, these data suggest that VMAT2 regulates in vivo glucose homeostasis and insulin production, most likely via its role in vesicular transport and storage of monoamines in beta-cells.
    Full-text · Article · Aug 2008 · Journal of Endocrinology
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