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Anti-tremor activity of talipexole produced by selective dopamine D2 receptor stimulation in cynomolgus monkeys with unilateral lesions in the ventromedial tegmentum
- Source :
- European Journal of Pharmacology. 319:197-205
- Publication Year :
- 1997
- Publisher :
- Elsevier BV, 1997.
-
Abstract
- The anti-tremor activity of talipexole (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine dihydrochloride, B-HT 920 CL2, Domin), a non-ergot dopamine D2 receptor agonist which possesses alpha 2-adrenoceptor agonistic and 5-HT3 receptor antagonistic properties, was examined in monkeys with a unilateral lesion in the ventromedial tegmentum. Talipexole dose dependently suppressed the tremor and had ED50 values of 34 micrograms/kg s.c. and 84 micrograms/kg p.o. The anti-tremor effect of talipexole occurred at much lower doses than that of an ergot dopamine receptor agonist, bromocriptine (2-bromo-alpha-ergocryptine mesilate, ED50; 2.5 mg/kg s.c.), and talipexole acted synergistically in combination with L-DOPA (3,4-dihydroxyphenylalanine). In ventromedial tegmentum-lesioned monkeys, anti-tremor doses of talipexole did not cause emetic behavior, but had sedative effects. Conversely, monkeys given bromocriptine exhibited oral movement, salivation and vomiting when anti-tremor effects were observed, but not marked sedative behavior at any of the doses investigated. During repeated administration of talipexole (a daily dose of 50 micrograms/kg s.c. for 21 days), the extent and duration of the anti-tremor effect did not change, but those of the sedative effect decreased gradually. The anti-tremor effect of talipexole was significantly suppressed by sulpiride, but not by SCH 23390 (7-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol) or yohimbine, while the sedative effect was inhibited by sulpiride and yohimbine. The main metabolites of talipexole had no anti-tremor or sedative effects. These results indicate that talipexole exerts its anti-tremor activity via selective dopamine D2 receptor stimulation.
- Subjects :
- Male
Agonist
medicine.medical_specialty
Tegmentum Mesencephali
medicine.drug_class
Injections, Subcutaneous
Dopamine Agents
Administration, Oral
Levodopa
chemistry.chemical_compound
Internal medicine
Dopamine receptor D2
Tremor
medicine
Animals
Hypnotics and Sedatives
Bromocriptine
Pharmacology
SCH-23390
Behavior, Animal
Receptors, Dopamine D2
Chemistry
Azepines
Talipexole
Yohimbine
Dopamine D2 Receptor Antagonists
Macaca fascicularis
Endocrinology
Dopamine receptor
Dopamine Agonists
Sulpiride
Adrenergic alpha-Agonists
medicine.drug
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 319
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....6b789f3c4a4f12b6c7f419dc135d8a62