Vol. 284, Issue 1, 307-311, 1998

Trihexyphenidyl Interactions with the Dopamine D₁-Selective Receptor Agonist SKF-82958 and the D₂-Selective Receptor Agonist N-0923 in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Hemiparkinsonian Monkeys¹

Edward F. Domino and Lisong Ni

Department of Pharmacology, University of Michigan, Ann Arbor, Michigan

The effects of the antiparkinsonian agent trihexyphenidyl, a selective M₁ muscarinic cholinergic receptor antagonist, were studied in doses of 100, 320 and 1000 µg/kg i.m. alone. Trihexyphenidyl was then studied in combination with the selective dopamine receptor D₁ agonist SKF-82958 [(±)-6-chloro-7-8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-benzazepine hydrobromide] and the selective D₂ agonist N-0923 [()2-(N-propyl-N-2-thienylethyl)amino-5-hydroxytetralin HCl] on rotational behavior in five 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned hemiparkinsonian monkeys. Given alone, trihexyphenidyl had no effect on ipsiversive and slightly enhanced contraversive circling. Contraversive circling produced by 74.8 and 234 µg/kg SKF-82958 i.m. was potentiated by increasing doses of trihexyphenidyl. On the other hand, contraversive circling produced by 10 and 32 µg/kg N-0923 i.m. was progressively reduced with increasing doses of trihexyphenidyl. The results obtained indicate differential actions on circling behavior between a selective M₁ muscarinic cholinergic receptor antagonist and selective D₁ and D₂ receptor agonists in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkey model of hemiparkinsonism.