title: (-)-OSU 6162 inhibits levodopa-induced dyskinesias in a monkey model of Parkinson's disease.
abstract: We have studied the effects of two D2 dopamine receptor-selective compounds, (-)-OSU 6162 and raclopride, on levodopa-induced dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmosets (Callithrix jacchus). Three monkeys developed a severe parkinsonian syndrome following administration of MPTP. In response to daily levodopa treatment the animals developed reproducible and idiosyncratic peak-dose dyskinesias. Pretreatment with (-)-OSU 6162 and raclopride, in doses increased by multiples of three, both dose-dependently relieved the levodopa-induced dyskinesias. However, in contrast to when raclopride pretreatment was given, (-)-OSU 6162 pretreatment did not induce akinesia. Our investigation suggests that (-)-OSU 6162 may be useful an an adjuvant treatment to levodopa in advanced Parkinson's disease to selectively combat levodopa-induced dyskinesias without affecting the antiparkinsonian response.
authors.affiliation: Department of Neurology, University Hospital, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Ekesbo
authors.forename: P E
authors.initials: PE
authors.lastname: Andrén
authors.forename: L M
authors.initials: LM
authors.lastname: Gunne
authors.forename: J
authors.initials: J
authors.lastname: Tedroff
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002144:Callithrix; D002230:Carbidopa / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000494:pharmacology; D007980:Levodopa / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D010880:Piperidines / Q000494:pharmacology*; D011187:Posture; D020891:Raclopride; D012457:Salicylamides / Q000494:pharmacology
chemical_list: D018492:Dopamine Antagonists; D010880:Piperidines; D012457:Salicylamides; C109513:OSU 6162; D020891:Raclopride; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002230:Carbidopa