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 L-dopa-induced dyskinesias, a debilitating side effect that develops in the majority of patients on L-dopa 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 L-dopa-induced dyskinesias.

Differential Involvement of D1 and D2 Dopamine Receptors in L-DOPA-Induced Angiogenic Activity in a Rat Model of Parkinson's Disease

“…Accordingly, microvascular responses ought to be considered when evaluating the effects of either anti-or pro-dyskinetic treatments with unknown mechanisms of action. Intriguingly, some vasoactive substances, such as a 2 -adrenergic receptor antagonists (Zou and Cowley, 2000), nicotine (Hawkins et al, 2002), and nitric oxide synthase inhibitors (Faraci and Brian, 1994) exert strong anti-dyskinetic effects in animal models of PD (Fox et al, 2001;Padovan-Neto et al, 2009;Quik et al, 2007Quik et al, , 2008. Elucidating the effects of these treatments on microvascular physiology and angiogenesis in the brain will be an exciting task for future studies.…”

Insights into the Neurobiology of the Nicotinic Cholinergic System and Nicotine Addiction from Mice Expressing Nicotinic Receptors Harboring Gain-of-Function Mutations

“…␣6-activating drugs could be combined with levodopa therapy to potentially allow lower doses of levadopa to effectively control PD symptoms. This approach could delay or fully prevent the development of levodopa-induced dyskinesias (Quik et al, 2008).…”

Nicotinic acetylcholine receptors and the ascending dopamine pathways

“…nAChRs present on afferents projecting to the VTA and SNc or to the terminal fields can also influence the activity of dopaminergic neurons. The nicotinic modulation of dopamine release has generated interest in nAChRs as therapeutic targets for conditions involving dopaminergic dysfunction, including schizophrenia, attention deficit hyperactivity disorder, Parkinson's disease, Alzheimer's disease and age-related cognitive impairment [7][8][9][10].…”