TRIHEXYPHENIDYL INTERACTIONS WITH THE DOPAMINE D-1-SELECTIVE RECEPTORAGONIST SKF-82958 AND THE D-2-SELECTIVE RECEPTOR AGONIST N-0923 IN METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE-INDUCED HEMIPARKINSONIAN MONKEYS

The effects of the antiparkinsonian agent trihexyphenidyl, a selective M-1 muscarinic cholinergic receptor antagonist, were studied in doses of 100, 320 and 1000 mu g/kg i.m. alone. Trihexyphenidyl was then stu died in combination with the selective dopamine receptor D-1 agonist S KF-82958 3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-benzazepine hydrobromi de] and the selective D-2 agonist N-0923 (N-propyl-N-2-thienylethyl)am ino-5-hydroxytetralin HCl] on rotational behavior in five ethyl-4-phen yl-1,2,3,6-tetrahydropyridine-lesioned hemiparkinsonian monkeys. Given alone, trihexyphenidyl had no effect on ipsiversive and slightly enha nced contraversive circling. Contraversive circling produced by 74.8 a nd 234 mu g/kg SKF-82958 i.m. was potentiated by increasing doses of t rihexyphenidyl. On the other hand, contraversive circling produced by 10 and 32 mu g/kg N-0923 i.m. was progressively reduced with increasin g doses of trihexyphenidyl. The results obtained indicate differential actions on circling behavior between a selective M-1 muscarinic choli nergic receptor antagonist and selective D-1 and D-2 receptor agonists in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkey model of h emiparkinsonism.