Transdermal nicotine in PD

Vieregge, Alexandra; Sieberer, Marcel; Jacobs, Helfried; Hagenah, Johann; Vieregge, P.

doi:10.1212/wnl.57.6.1032

Cited by 124 publications

(88 citation statements)

References 17 publications

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“…To date, administration of the nicotine patch and/or gum has yielded conflicting results, with some studies reporting small improvements in motor and cognitive deficits and others no effect or a decline (Ishikawa and Miyatake, 1993;Fagerstrom et al, 1994;Ebersbach et al, 1999;Kelton et al, 2000;Vieregge et al, 2001;Lemay et al, 2004). Drawbacks of these studies include the limited number of subjects and very short duration (2-4 weeks).…”

Section: Discussionmentioning

confidence: 99%

Chronic Oral Nicotine Normalizes Dopaminergic Function and Synaptic Plasticity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Primates

Quik

Chen²,

Parameswaran³

et al. 2006

J. Neurosci.

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Our recent studies show that chronic oral nicotine partially protects against striatal damage in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primates. To identify the cellular changes associated with this protective action, we investigated the effects of nicotine treatment on stimulus-evoked dopamine release, dopamine turnover, and synaptic plasticity in striatum from lesioned and unlesioned animals. Monkeys were chronically (6 months) treated with nicotine in the drinking water and subsequently lesioned with the dopaminergic neurotoxin MPTP (6 months) while nicotine was continued. Nigrostriatal damage increased nicotinic acetylcholine receptor (nAChR)-mediated fractional dopamine release from residual terminals, primarily through changes in ␣3*/␣6* nAChRs. In contrast, fractional receptor-evoked dopamine release was similar to control in unlesioned and lesioned animals with chronic oral nicotine. Long-term nicotine administration also attenuated the enhanced K ϩ -evoked fractional dopamine release from synaptosomes of MPTP-lesioned animals, suggesting that nicotine treatment had a generalized effect on dopaminergic function. This premise was further supported by experiments showing that nicotine dosing decreased the elevated dopamine turnover that occurs after nigrostriatal damage. We next investigated changes in synaptic plasticity with lesioning and nicotine treatment. Nicotine treatment alone enhanced synaptic plasticity by lowering the threshold for long-term depression (LTD) in the corticostriatal pathway. MPTP lesioning led to a loss of LTD, a measure of short-term synaptic plasticity. In contrast, LTD was preserved in nicotine-treated lesioned animals. Thus, the present data show that the disruptions in striatal dopaminergic function after nigrostriatal damage were attenuated with chronic nicotine administration. These cellular alterations may underlie the ability of nicotine to maintain/restore normal function with nigrostriatal damage.

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Section: Discussionmentioning

confidence: 99%

Chronic Oral Nicotine Normalizes Dopaminergic Function and Synaptic Plasticity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Primates

Quik

Chen²,

Parameswaran³

et al. 2006

J. Neurosci.

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“…Based on the apparent protective effect of smoking, the therapeutic effect of nicotine has been tested in a few clinical trials, but no improvement of motor symptoms with transdermal nicotine treatment has been documented [668,669]. Moreover, on the basis of the apparent protective effect of coffee in PD, adenosine receptor (A 2A ) antagonists have also been tested and there is evidence that they improve parkinsonian symptoms in animal models [670] and clinical trials [671][672][673][674].…”

Section: Comments and Perspectivesmentioning

confidence: 99%

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

et al. 2011

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“…Kelton and co-workers [52] observed improvements in areas of cognitive performance and motor measures after treatment with intravenous nicotine and the nicotine patch, with effects sustained for up to 1 month after the drug. However, Vieregge et al observed no improvements in patients administered the patch for 3 weeks [53], although the lack of efficacy may have related to the fact that Parkinsonism was only assessed 3 weeks after patch cessation. On the other hand, Lemay et al [54] also obtained no improvement in motor or cognitive deficits with immediate testing of Parkinson's disease symptoms after 3 to 4 weeks of treatment.…”

Section: Nicotine and Nicotinic Agonists For The Symptomatic Treatmenmentioning

confidence: 99%

Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

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Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal α6β2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, α4β2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to α6β2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics. Keywordsα-ConotoxinMII; Nicotine; Nicotinic; Parkinson's disease; Nigrostriatal; Striatum Parkinson's disease and the nicotinic cholinergic systemThe pathological hallmarks of Parkinson's disease are the presence of intracellular Lewy bodies and an extensive degeneration of the nigrostriatal dopaminergic system. [1][2][3][4]. There is a ≥70% decline in striatal dopamine and ≥50% loss of nigral dopaminergic neurons with the onset of clinical symptoms, which include bradykinesia, rigidity, and tremor [1][2][3][4].Although Parkinson's disease has primarily been considered a dopaminergic disorder, it is becoming increasingly clear that multiple CNS systems are involved in its pathogenesis [5][6][7]. Braak and coworkers have also identified Lewy bodies in numerous non-dopaminergic brain regions including the locus coeruleus, raphe nuclei, thalamus, amygdala, olfactory nuclei, pedunculopontine nucleus, and cerebral cortex [5,6]. These observations are in agreement with much earlier studies, which indicated that multiple CNS neuronal systems are affected in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the...

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Transdermal nicotine in PD

Abstract: With the dosage and the period of treatment chosen, transdermal nicotine patches are not effective as an add-on treatment for symptoms of PD.

Cited by 124 publications

References 17 publications

Chronic Oral Nicotine Normalizes Dopaminergic Function and Synaptic Plasticity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Primates

Chronic Oral Nicotine Normalizes Dopaminergic Function and Synaptic Plasticity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Primates

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

Nicotinic receptors as CNS targets for Parkinson's disease

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