There is no generally accepted treatment for tardive dyskinesia following intake of neuroleptics. Many compounds with effects on serotonine, GABA, cholinergic or dopamine receptors have been clinically useful. We report on a 71-year-old female patient suffering from orofacial tardive dyskinesia after treatment with haloperidol, which did not respond to monotherapy with antidyskinetic drugs. The syndrome disappeared almost completely within two weeks after a multidrug approach consisting of tetrabenazine, olanzapine and tiapride. A combination of antidyskinetic drugs should be considered in patients with severe tardive dyskinesia.
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Neuropsychopharmacology
January 2025
Neurocrine Biosciences, Inc., San Diego, CA, USA.
Positron emission tomography (PET) is frequently used to obtain target occupancy (%TO) of central nervous system (CNS) drug candidates during clinical development. Obtaining %TO with PET can be particularly powerful when the %TO associated with efficacy is known for a protein target. Using the radiotracer [F]AV-133, the relationship between plasma concentration (PK) and %TO of NBI-750142, an experimental inhibitor of the vesicular monoamine transporter type 2 (VMAT2) was obtained in both nonhuman primate (NHP) and human.
View Article and Find Full Text PDFNat Commun
January 2025
Shanghai Fifth People's Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Vesicular monoamine transporter 2 (VMAT2) is crucial for packaging monoamine neurotransmitters into synaptic vesicles, with their dysregulation linked to schizophrenia, mood disorders, and Parkinson's disease. Tetrabenazine (TBZ) and valbenazine (VBZ), both FDA-approved VMAT2 inhibitors, are employed to treat chorea and tardive dyskinesia (TD). Our study presents the structures of VMAT2 bound to substrates serotonin (5-HT) and dopamine (DA), as well as the inhibitors TBZ and VBZ.
View Article and Find Full Text PDFExpert Opin Pharmacother
December 2024
Department of Neurology, UTHealth Houston McGovern Medical School, Houston, TX, USA.
Introduction: Chorea is a motor manifestation of Huntington's disease (HD), which can lead to decreased functional independence and falls. Even though multiple classes of medications have been used to treat this symptom, only the vesicular monoamine transporter 2 (VMAT2) inhibitors tetrabenazine, deutetrabenazine, and valbenazine have been approved by the FDA for this indication.
Areas Covered: This article reviews the pharmacological properties, clinical efficacy, safety, and tolerability of valbenazine in the treatment of chorea in HD.
Ment Health Clin
December 2024
(Corresponding author) Clinical Pharmacist Specialist, Vanderbilt Specialty Pharmacy Services, Nashville, Tennessee,
Vesicular monoamine transporter 2 inhibitors (VMAT2i) are currently Food and Drug Administration-approved for the treatment of Huntington disease chorea and tardive dyskinesia. Additionally, they are often used for other hyperkinetic movement disorders in clinical practice. Due to a lack of head-to-head clinical trials, management of VMAT2i in the clinical setting may be unclear and rely on the clinical experience of the practitioner.
View Article and Find Full Text PDFNeurotox Res
December 2024
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Chronic use of typical antipsychotics can lead to varying motor effects depending on the timing of analysis. Acute treatment typically induces hypokinesia, resembling parkinsonism, while repeated use can result in tardive dyskinesia, a hyperkinetic syndrome marked by involuntary orofacial movements, such as vacuous chewing movements in mice. Tardive dyskinesia is particularly concerning due to its potential irreversibility and associated motor discomfort.
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