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.
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.
Department of Pharmacology, University of Michigan, Ann Arbor, MI 49109-0632, United States. efdabcde@umich.edu
Edward F
EF
Domino
Lisong
L
Ni
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D001712:Biperiden / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D007980:Levodopa / Q000031:analogs & derivatives* / Q000494:pharmacology; D008254:Macaca nemestrina; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3 / Q000819:agonists; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D000978:Antiparkinson Agents; D001552:Benzazepines; D018491:Dopamine Agonists; D018727:Muscarinic Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D001712:Biperiden; D007980:Levodopa; C071262:SK&F 82958; C047508:rotigotine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C035420:levodopa methyl ester