Abstract |
We examined whether or not the antiparkinsonian activity of talipexole ( B-HT 920, 6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]-azepine) could be optimised by combination with L-3,4-dihydroxyphenylalanine ( L-dopa). Additionally, the effects of chronic treatment with talipexole on motor behavior were investigated using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( MPTP)-treated and normal common marmosets. Administration of MPTP (0.5 mg/animal i.v. once or twice) to marmosets induced persistent parkinsonian motor deficits. The antiparkinsonian activity of talipexole (40 micrograms/kg s.c.) was significantly enhanced by its combination with L-dopa (30 mg/kg i.p.). This may further support the postulated postsynaptic dopamine D2 receptor agonist properties of talipexole. Chronic treatment with talipexole (a daily dose of 40 micrograms/kg s.c. for 21 days) did not lead to tolerance to the antiparkinsonian activity in MPTP-treated animals. No obvious dyskinesia was seen throughout the chronic treatment. In contrast, in normal marmosets, talipexole at a dose of 80 micrograms/kg which is a dose sufficient to induce hyperactivity did not increase motor activity during the treatment repeated for 21 days. These results suggest that talipexole is a selective dopamine D2 receptor agonist drug of potential use in the treatment of Parkinson's disease.
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Authors | M Irifune, M Nomoto, T Fukuda |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 264
Issue 2
Pg. 117-23
(Oct 24 1994)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 7851473
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Antiparkinson Agents
- Azepines
- Dopamine Agonists
- Levodopa
- talipexole
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Topics |
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(administration & dosage)
- Analysis of Variance
- Animals
- Antiparkinson Agents
(administration & dosage, pharmacology, therapeutic use)
- Azepines
(administration & dosage, pharmacology, therapeutic use)
- Callithrix
- Disease Models, Animal
- Dopamine Agonists
(administration & dosage, pharmacology, therapeutic use)
- Dose-Response Relationship, Drug
- Drug Therapy, Combination
- Female
- Injections, Intraperitoneal
- Injections, Intravenous
- Injections, Subcutaneous
- Levodopa
(administration & dosage, pharmacology, therapeutic use)
- MPTP Poisoning
- Male
- Motor Activity
(drug effects)
- Parkinson Disease, Secondary
(chemically induced, drug therapy)
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