Abstract | BACKGROUND: The efficacy of the dopaminergic stabilizer, pridopidine, in reducing the voluntary and involuntary motor symptoms of Huntington's disease (HD) is under clinical evaluation. Tetrabenazine is currently the only approved treatment for chorea, an involuntary motor symptom of HD; both compounds influence monoaminergic neurotransmission. OBJECTIVE: METHODS: RESULTS: Monitoring for 1 hour after co-administration of tetrabenazine 0.64 mg/kg and pridopidine 32 mg/kg revealed a reduction in locomotor activity, measured as distance travelled, in the tetrabenazine treated group, down to 61% vs. vehicle controls (p < 0.001). This was significantly alleviated by pridopidine (distance travelled reached 137% vs. tetrabenazine controls, p < 0.01). In contrast, co-administration of haloperidol 0.12 mg/kg and tetrabenazine produced increased inhibition of locomotor activity over the same period (p < 0.01, 41% vs. tetrabenazine). Co-administration of pridopidine, 10.5 mg/kg or 32 mg/kg, with tetrabenazine counteracted significantly (p < 0.05) and dose-dependently the decrease in frontal cortex Arc levels induced by tetrabenazine 0.64 mg/kg ( Arc mRNA reached 193% vs. tetrabenazine mean at 32 mg/kg); this counteraction was not seen with haloperidol. Tetrabenazine retained its characteristic neurochemical effects of increased striatal DOPAC and reduced striatal dopamine when co-administered with pridopidine. CONCLUSIONS:
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Authors | Susanna Waters, Henrik Ponten, Daniel Klamer, Nicholas Waters |
Journal | Journal of Huntington's disease
(J Huntingtons Dis)
Vol. 3
Issue 3
Pg. 285-98
( 2014)
ISSN: 1879-6400 [Electronic] Netherlands |
PMID | 25300332
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Drug Combinations
- Piperidines
- pridopidine
- Dopamine
- Tetrabenazine
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Topics |
- Animals
- Behavior, Animal
(drug effects, physiology)
- Corpus Striatum
(drug effects, metabolism)
- Dopamine
(metabolism)
- Dose-Response Relationship, Drug
- Drug Combinations
- Drug Interactions
- Locomotion
(drug effects, physiology)
- Male
- Motor Activity
(drug effects, physiology)
- Piperidines
(administration & dosage)
- Rats
- Rats, Sprague-Dawley
- Tetrabenazine
(administration & dosage)
- Treatment Outcome
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