Abstract
The effects of biperiden (0, 100, and 320 µg/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 µg/kg), or a selective D 2/D 3 receptor agonist rotigotine (32 µg/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.
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