title: Nicotine reduces established levodopa-induced dyskinesias in a monkey model of Parkinson's disease.
abstract: Although 3,4-dihydroxyphenylalanine (levodopa) is the gold-standard treatment for Parkinson's disease, it can lead to disabling dyskinesias. Previous work demonstrated that nicotine reduces levodopa-induced dyskinesias (LIDs) in several parkinsonian animal models. The goal of this study was to determine whether the duration of nicotine administration affects its ability to reduce LIDs in levodopa-primed and levodopa-naíve monkeys and also to test whether tolerance develops to the beneficial effects of nicotine. Monkeys were injected with MPTP (1.9-2.0 mg/kg subcutaneously) over 3 to 5 months until parkinsonism developed. Nicotine (300 μg/mL) was administered in drinking water (over 4-6 months) to levodopa-primed or levodopa-naíve monkeys, with levodopa/carbidopa (10/2.5 mg/kg) gavaged twice daily. One set of MPTP-lesioned monkeys (n = 23) was first gavaged with levodopa and subsequently received nicotine 4 weeks later, when dyskinesias plateaued, or 8 weeks later, when dyskinesias were established. A 60% to 70% decrease in LIDs was observed after several weeks of nicotine treatment in both groups. A second set of monkeys (n = 26) received nicotine 8 or 2 weeks before levodopa. In the 8-week nicotine pretreatment group, there was an immediate reduction in LIDs, which plateaued at 60% to 70%. In the 2-week nicotine pretreatment group, there were initial small decreases in LIDs, which plateaued at 60% to 70% several weeks later. Thus, nicotine pretreatment and nicotine post-treatment were similarly efficacious in reducing LIDs. The beneficial effect of nicotine persisted throughout the study (17-23 weeks). Nicotine did not worsen parkinsonism. These data suggest that nicotine treatment has potential as a successful antidyskinetic therapy for patients with Parkinson's disease.
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, California, USA.
authors.forename: Maryka
authors.initials: M
authors.lastname: Quik
authors.forename: Archana
authors.initials: A
authors.lastname: Mallela
authors.forename: Jason
authors.initials: J
authors.lastname: Ly
authors.forename: Danhui
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018726:Anti-Dyskinesia Agents; D000978:Antiparkinson Agents; D003367:Cotinine / Q000097:blood; D003627:Data Interpretation, Statistical; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D005260:Female; D007980:Levodopa; D020267:MPTP Poisoning / Q000188:drug therapy; D008297:Male; D009538:Nicotine / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D012453:Saimiri
chemical_list: D018726:Anti-Dyskinesia Agents; D000978:Antiparkinson Agents; D018722:Nicotinic Agonists; D007980:Levodopa; D009538:Nicotine; D003367:Cotinine
keywords: Parkinson's disease; dyskinesia; levodopa; nicotine; nicotinic; nonhuman primate