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 monkeys.
The effects of the antiparkinsonian agent trihexyphenidyl, a selective M1 muscarinic cholinergic receptor antagonist, were studied in doses of 100, 320 and 1000 micrograms/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 micrograms/kg SKF-82958 i.m. was potentiated by increasing doses of trihexyphenidyl. On the other hand, contraversive circling produced by 10 and 32 micrograms/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.
Domino
E F
EF
Department of Pharmacology, University of Michigan, Ann Arbor, USA.
Ni
L
L
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001552:Benzazepines / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D020267:MPTP Poisoning; D008254:Macaca nemestrina; D010302:Parkinson Disease, Secondary / Q000188:drug therapy*; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D014282:Trihexyphenidyl / Q000627:therapeutic use*
D000978:Antiparkinson Agents; D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D014282:Trihexyphenidyl; C071262:SK&F 82958; C047508:rotigotine