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Current Evidence for Neuroprotective Effects of Nicotine and Caffeine Against Parkinson’s Disease

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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting 1 to 3% of individuals over the age of 65 years. While effective therapy exists for treating the bradykinesia, rigidity and tremor associated with the disease, the cause is unknown. There is no treatment available to prevent or slow the progressive neuronal loss in the substantia nigra and associated decreased levels of dopamine in the striatum that underlie the cardinal features of the disease.

Both retrospective and prospective epidemiological studies have consistently demonstrated an inverse association between cigarette smoking and PD, leading to theories that smoking in general and nicotine in particular might be neuroprotective. Nicotine has been shown in animals to stimulate the release of dopamine in the striatum, and to preserve nigral neurons and striatal dopamine levels in laboratory animals with lesioned nigrostriatal pathways.

Coffee and caffeine consumption have also been shown in epidemiological studies to be inversely related to PD risk. Caffeine is an adenosine A2A receptor antagonist that enhances locomotor activity in animal models of parkinsonism. Theophylline, a related compound that has A2A receptor blocking properties, has been shown in one small trial to improve motor function in patients with PD.

Recently, potent and highly selective A2A receptor antagonists have been developed that have demonstrated improvement in motor function in animal models of parkinsonism. Exciting findings are emerging that demonstrate attenuation of dopaminergic neurotoxicity with caffeine and other adenosine receptor antagonists in mice given the neurotoxin l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP), suggesting that these compounds may be neuroprotective.

Evidence for the neuroprotective potential of nicotine and caffeine is compelling, but further work is needed before testing these and related compounds in clinical trials for both individuals at high risk of developing PD and those with early, untreated disease.

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Acknowledgements

The author’s work cited in this paper was supported by US Department of the Army grant DAMD17-98-1-8621; National Institute on Aging contract N01-AG-4-2149; and Office of Research and Development Medical Research Service, Department of Veterans Affairs. The information contained in this article does not necessarily reflect the position or the policy of the government, and no official endorsement should be inferred.

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  1. Department of Veterans Affairs, Honolulu, Hawaii, USA

    G. Webster Ross & Helen Petrovitch

  2. The Parkinson’s Institute, Sunnyvale, California, USA

    G. Webster Ross

  3. Pacific Health Research Institute, 846 South Hotel Street, Suite 307, Honolulu, Hawaii, 96813, USA

    G. Webster Ross & Helen Petrovitch

  4. University of Hawaii John A. Burns School of Medicine, Honolulu, Hawaii, USA

    G. Webster Ross & Helen Petrovitch

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Ross, G.W., Petrovitch, H. Current Evidence for Neuroprotective Effects of Nicotine and Caffeine Against Parkinson’s Disease. Drugs Aging 18, 797–806 (2001). https://doi.org/10.2165/00002512-200118110-00001

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