Nicotine and Parkinson's disease: implications for therapy

Abstract

Accumulating evidence suggests that nicotine, a drug that stimulates nicotinic acetylcholine receptors, may be of therapeutic value in Parkinson's disease. Beneficial effects may be several-fold. One of these is a protective action against nigrostriatal damage. This possibility stems from the results of epidemiological studies that consistently demonstrate an inverse correlation between tobacco use and Parkinson's disease. This reduced incidence of Parkinson's disease has been attributed to the nicotine in tobacco products, at least in part, based on experimental work showing a protective effect of nicotine against toxic insults. Second, several studies suggest a symptomatic effect of nicotine in Parkinson's disease, although effects are small and somewhat variable. Third, recent data in nonhuman primates show that nicotine attenuates levodopa-induced dyskinesias, a debilitating side effect that develops in the majority of patients on levodopa therapy. Collectively, these observations suggest that nicotine or CNS selective nicotinic receptor ligands hold promise for Parkinson's disease therapy to reduce disease progression, improve symptoms, and/or decrease levodopa-induced dyskinesias.

FIG. 1

Nicotine treatment reduces L-dopa-induced dyskinesias in nonhuman primates . Time course of the nicotine-induced decline in levodopa-induced dyskinesias (top panel). MPTP-lesioned monkeys were given either nicotine or vehicle for several weeks and then gavaged with levodopa (L-dopa, 5 mg/kg) twice daily. Each symbol is the mean ± SE of 3 to 4 monkeys. Dyskinesias were significantly reduced in nicotine-treated animals compared to monkeys not receiving nicotine (p < 0.01) using a Mann-Whitney test. Total dyskinesias were significantly decreased by nicotine treatment after both the morning and afternoon dose of L-dopa (middle panel). **p < 0.01 depicts a main effect of nicotine by two-way ANOVA. Nicotine treatment did not affect parkinsonism either on or off L-dopa (lower panel). **p < 0.01 as compared to the same group with no levodopa treatment by a Mann-Whitney test.