| Title | Biperiden enhances L-DOPA methyl ester and dopamine D(l) receptor agonist SKF-82958 but antagonizes D(2)/D(3) receptor agonist rotigotine antihemiparkinsonian actions. | | Author(s) | Domino EF, Ni L | | Institution | Department of Pharmacology, University of Michigan, Ann Arbor, MI 49109-0632, United States. efdabcde@umich.edu | | Source | Eur J Pharmacol 2008 Dec 3; 599(1-3):81-5. | | MeSH | 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Antiparkinson Agents
Behavior, Animal
Benzazepines
Biperiden
Disease Models, Animal
Dopamine Agonists
Dose-Response Relationship, Drug
Drug Interactions
Female
Levodopa
Macaca nemestrina
Muscarinic Antagonists
Parkinsonian Disorders
Receptors, Dopamine D1
Receptors, Dopamine D2
Receptors, Dopamine D3
Tetrahydronaphthalenes
Thiophenes
| | Abstract | The effects of biperiden (0, 100, and 320 microg/kg), a selective muscarinic M(1)/M(4) receptor cholinergic antagonist, were studied alone and in combination with those of L-DOPA methyl ester (16.7 mg/kg), a selective dopamine D(1) receptor agonist SKF-82958 (74.8 microg/kg), or a selective D(2)/D(3) receptor agonist rotigotine (32 microg/kg) on circling behavior in MPTP induced hemiparkinsonian monkeys. The doses selected were given i.m. in approximately equieffective doses to produce contraversive circling. Biperiden alone with 5% dextrose vehicle produced a slight increase in contraversive circling in a dose related manner. When combined with L-DOPA methyl ester, it enhanced contraversive circling and decreased ipsiversive circling. When biperiden was combined with SKF-82958, contraversive circling also was enhanced and ipsiversive circling decreased. Exactly the opposite was observed with the combination of biperiden and rotigotine. The results indicate a dramatic difference in effects of a prototypic muscarinic M(1)/M(4) receptor cholinergic antagonist in combination with prototypic full dopamine D(1) or D(2)/D(3) receptor agonists. Biperiden interactions with L-DOPA methyl ester were more predominantly D(l) than D(2)/D(3) receptor-like in this animal model of hemiparkinsonism. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 18851961 |
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