Kathryn Leary

Publications (2)15.59 Total impact

• Article: Nicotine and Parkinson's disease: Implications for therapy

  Maryka Quik PhD, O&apos, Kathryn Leary, Caroline M. Tanner, Maryka Quik, Kathryn O'Leary
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  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. © 2007 Movement Disorder Society
  Movement Disorders 08/2008; 23(12):1641 - 1652. · 4.51 Impact Factor
• Article: Nicotine reduces levodopa‐induced dyskinesias in lesioned monkeys

  Maryka Quik PhD, Heather Cox, Neeraja Parameswaran, O&apos, Kathryn Leary, J. William Langston, Donato Di Monte, Maryka Quik, Kathryn O'Leary
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  ABSTRACT: Objective Levodopa, the gold standard for Parkinson's disease treatment, is associated with debilitating abnormal involuntary movements or dyskinesias, for which few treatments are currently available. Studies have implicated numerous neurotransmitters in the development of levodopa-induced dyskinesias. However, the cholinergic system has received little attention despite an extensive overlap between dopaminergic terminals and cholinergic interneurons in the striatum and the well-known ability of nicotine to stimulate striatal dopamine release. Our objective, therefore, was to determine whether nicotine treatment reduced levodopa-induced dyskinesias.Methods The effect of nicotine (provided in the drinking water) was determined on dyskinesias induced by levodopa (5mg/kg twice daily by oral gavage) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–treated monkeys.ResultsNicotine pretreatment reduced peak and total levodopa-induced dyskinesias in levodopa-naive monkeys over an 8-week period, with a decrease in total dyskinesias of about 50%. A crossover study was then done in which levodopa-treated monkeys originally receiving vehicle were administered nicotine, whereas the levodopa-treated animals initially receiving nicotine were placed on vehicle. Nicotine treatment to levodopa-primed monkeys led to an approximately 35% reduction in total dyskinesias that lasted for at least 8 weeks, at which time the study was ended. In contrast, a significant increase in levodopa-induced dyskinesias was observed in the group of animals that had previously received nicotine and were then switched to vehicle. Nicotine treatment did not appear to affect the antiparkinsonian action of levodopa.InterpretationThese data suggest that nicotine or selective nicotinic agonists may represent a useful treatment strategy to reduce levodopa-induced dyskinesias. Ann Neurol 2007
  Annals of Neurology 11/2007; 62(6):588 - 596. · 11.09 Impact Factor