Histamine H3 receptor agonists reduce L‐dopa–induced chorea, but not dystonia, in the MPTP‐lesioned nonhuman primate model of Parkinson's disease
Identifieur interne : 004716 ( Main/Merge ); précédent : 004715; suivant : 004717Histamine H3 receptor agonists reduce L‐dopa–induced chorea, but not dystonia, in the MPTP‐lesioned nonhuman primate model of Parkinson's disease
Auteurs : Jordi Gomez-Ramirez [Canada] ; Tom H. Johnston [Canada] ; Naomi P. Visanji [Canada] ; Susan H. Fox [Canada] ; Jonathan M. Brotchie [Canada]Source :
- Movement Disorders [ 0885-3185 ] ; 2006-06-06.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Callithrix, Chorea (chemically induced), Chorea (prevention & control), Disease Models, Animal, Female, Histamine Agonists (pharmacology), Levodopa (adverse effects), L‐dopa–induced dyskinesia, MPTP‐lesioned marmoset, Parkinson Disease (drug therapy), Parkinson Disease (physiopathology), Parkinson's disease, Receptors, Histamine H3 (physiology), histamine H3 receptor agonist.
- MESH :
- chemical , adverse effects : Levodopa.
- chemical , pharmacology : Histamine Agonists.
- chemical , physiology : Receptors, Histamine H3.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemically induced : Chorea.
- drug therapy : Parkinson Disease.
- physiopathology : Parkinson Disease.
- prevention & control : Chorea.
- Animals, Callithrix, Disease Models, Animal, Female.
Abstract
L‐dopa–induced dyskinesia (LID) remains a major complication of the treatment of Parkinson's disease. The neural mechanisms underlying LID are thought to involve overactivity of striatal glutamatergic neurotransmission, with resultant underactivation of the output regions of the basal ganglia. Histamine H3 heteroreceptors can reduce glutamate and γ‐aminobutyric acid (GABA) transmission in the striatum and substantia nigra reticulata, respectively. Thus, we tested whether the histamine H3 receptor agonists immepip and imetit can alleviate LID in the MPTP‐lesioned marmoset model of Parkinson's disease. Coadministration of immepip (1 mg/kg) with L‐dopa (15 mg/kg) was associated with significantly less total dyskinesia than L‐dopa alone. When dyskinesia was separately rated as chorea and dystonia, coadministration of L‐dopa with either immepip or imetit (both 10 mg/kg) significantly reduced chorea but had no effect on dystonia. The antidyskinetic actions of the H3 agonists were not accompanied by alteration of the antiparkinsonian actions of L‐dopa. However, immepip (10 mg/kg), when administered as monotherapy, significantly increased parkinsonian disability compared to vehicle. Overall, the results obtained in this study suggest that histamine H3 receptors may be involved in the neural mechanisms underlying L‐dopa–induced dyskinesia in Parkinson's disease. © 2006 Movement Disorder Society
Url:
DOI: 10.1002/mds.20828
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ISTEX:855A426357D319975E05A256C1724337E8331864Le document en format XML
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<front><div type="abstract" xml:lang="en">L‐dopa–induced dyskinesia (LID) remains a major complication of the treatment of Parkinson's disease. The neural mechanisms underlying LID are thought to involve overactivity of striatal glutamatergic neurotransmission, with resultant underactivation of the output regions of the basal ganglia. Histamine H3 heteroreceptors can reduce glutamate and γ‐aminobutyric acid (GABA) transmission in the striatum and substantia nigra reticulata, respectively. Thus, we tested whether the histamine H3 receptor agonists immepip and imetit can alleviate LID in the MPTP‐lesioned marmoset model of Parkinson's disease. Coadministration of immepip (1 mg/kg) with L‐dopa (15 mg/kg) was associated with significantly less total dyskinesia than L‐dopa alone. When dyskinesia was separately rated as chorea and dystonia, coadministration of L‐dopa with either immepip or imetit (both 10 mg/kg) significantly reduced chorea but had no effect on dystonia. The antidyskinetic actions of the H3 agonists were not accompanied by alteration of the antiparkinsonian actions of L‐dopa. However, immepip (10 mg/kg), when administered as monotherapy, significantly increased parkinsonian disability compared to vehicle. Overall, the results obtained in this study suggest that histamine H3 receptors may be involved in the neural mechanisms underlying L‐dopa–induced dyskinesia in Parkinson's disease. © 2006 Movement Disorder Society</div>
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<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term>
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<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Chorea</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Callithrix</term>
<term>Disease Models, Animal</term>
<term>Female</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">L-dopa-induced dyskinesia (LID) remains a major complication of the treatment of Parkinson's disease. The neural mechanisms underlying LID are thought to involve overactivity of striatal glutamatergic neurotransmission, with resultant underactivation of the output regions of the basal ganglia. Histamine H3 heteroreceptors can reduce glutamate and gamma-aminobutyric acid (GABA) transmission in the striatum and substantia nigra reticulata, respectively. Thus, we tested whether the histamine H3 receptor agonists immepip and imetit can alleviate LID in the MPTP-lesioned marmoset model of Parkinson's disease. Coadministration of immepip (1 mg/kg) with L-dopa (15 mg/kg) was associated with significantly less total dyskinesia than L-dopa alone. When dyskinesia was separately rated as chorea and dystonia, coadministration of L-dopa with either immepip or imetit (both 10 mg/kg) significantly reduced chorea but had no effect on dystonia. The antidyskinetic actions of the H3 agonists were not accompanied by alteration of the antiparkinsonian actions of L-dopa. However, immepip (10 mg/kg), when administered as monotherapy, significantly increased parkinsonian disability compared to vehicle. Overall, the results obtained in this study suggest that histamine H3 receptors may be involved in the neural mechanisms underlying L-dopa-induced dyskinesia in Parkinson's disease.</div>
</front>
</TEI>
</PubMed>
</double>
</record>
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