Tetrabenazine-induced depletion of brain monoamines: Mechanism by which desmethylimipramine protects cortical norepinephrine

Pettibone, D. J.; Pflueger, A. Barbara; Totaro, James A.

doi:10.1016/0014-2999(84)90563-6

Cited by 25 publications

(13 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TBZ depletes dopamine more selectively over norepinephrine and serotonin by inhibiting transport into presynaptic vesicles [12,13]. The highest binding density for TBZ is in the caudate nucleus, putamen and nucleus accumbens, areas known to bear the brunt of pathology in HD [14,15].…”

Section: Introductionmentioning

confidence: 99%

Tetrabenazine as anti-chorea therapy in Huntington Disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators

Frank

2009

BMC Neurol

145

View full text Add to dashboard Cite

BackgroundTetrabenazine (TBZ) selectively depletes central monoamines by reversibly binding to the type-2 vesicular monoamine transporter. A previous double blind study in Huntington disease (HD) demonstrated that TBZ effectively suppressed chorea, with a favorable short-term safety profile (Neurology 2006;66:366-372). The objective of this study was to assess the long-term safety and effectiveness of TBZ for chorea in HD.MethodsSubjects who completed the 13-week, double blind protocol were invited to participate in this open label extension study for up to 80 weeks. Subjects were titrated to the best individual dose or a maximum of 200 mg/day. Chorea was assessed using the Total Maximal Chorea (TMC) score from the Unified Huntington Disease Rating Scale.ResultsOf the 75 participants, 45 subjects completed 80 weeks. Three participants terminated due to adverse events (AEs) including depression, delusions with associated previous suicidal behavior, and vocal tics. One subject died due to breast cancer. The other 26 subjects chose not to continue on with each ensuing extension for various reasons. When mild and unrelated AEs were excluded, the most commonly reported AEs (number of subjects) were sedation/somnolence (18), depressed mood (17), anxiety (13), insomnia (10), and akathisia (9). Parkinsonism and dysphagia scores were significantly increased at week 80 compared to baseline. At week 80, chorea had significantly improved from baseline with a mean reduction in the TMC score of 4.6 (SD 5.5) units. The mean dosage at week 80 was 63.4 mg (range 12.5-175 mg).ConclusionsTBZ effectively suppresses HD-related chorea for up to 80 weeks. Patients treated chronically with TBZ should be monitored for parkinsonism, dysphagia and other side effects including sleep disturbance, depression, anxiety, and akathisia.Trial RegistrationClinicaltrials.gov registration number (initial study): NCT00219804

show abstract

Section: Introductionmentioning

confidence: 99%

Tetrabenazine as anti-chorea therapy in Huntington Disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators

Frank

2009

BMC Neurol

145

View full text Add to dashboard Cite

show abstract

“…There is a recent review of the development and uses of tetrabenazine [62]. By reversibly inhibiting the central vesicular monoamine transporter type 2, TBZ more selectively depletes dopamine than norepinephrine [48,63]. The highest binding density for TBZ is in the caudate nucleus, putamen, and nucleus accumbens, areas known to be most affected in HD [64,65].…”

Section: Pharmacological Treatment Optionsmentioning

confidence: 99%

Treatment of Huntington's Disease

2014

View full text Add to dashboard Cite

“…56 First introduced in 1956 as an antipsychotic drug, 57 TBZ is currently used to treat hyperkinetic movement disorders, such as chorea associated with Huntington ' s disease, tics in Tourette ' s syndrome, and movement stereotypes in tardive dyskinesia. [58][59][60] The side effects associated with TBZ include sedation, depression, akathisia, and parkinsonism.…”

Section: Tbz and Its Analogsmentioning

confidence: 99%