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: Maryka Quik, Archana Mallela, Jason Ly, Danhui Zhang
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 28 Issue 10 Pg. 1398-406 (Sep 2013) ISSN: 1531-8257 [Electronic] United States
• PMID: 23836409 (Publication Type: Journal Article)
• Copyright: © 2013 International Parkinson and Movement Disorder Society.

Chemical References

• Anti-Dyskinesia Agents
• Antiparkinson Agents
• Nicotinic Agonists
• Levodopa
• Nicotine
• Cotinine

Topics

• Animals
• Anti-Dyskinesia Agents
• Antiparkinson Agents
• Cotinine (blood)
• Data Interpretation, Statistical
• Dyskinesia, Drug-Induced (drug therapy)
• Female
• Levodopa
• MPTP Poisoning (drug therapy)
• Male
• Nicotine (therapeutic use)
• Nicotinic Agonists (therapeutic use)
• Parkinson Disease, Secondary (chemically induced, drug therapy)
• Saimiri