Elsevier

Life Sciences

Volume 50, Issue 25, 1992, Pages PL233-PL237
Life Sciences

Pharmacology letters
Inhibition of [3H]dopamine uptake into rat striatal slices by quaternary n-methylated nicotine metabolites

https://doi.org/10.1016/0024-3205(92)90533-UGet rights and content

Abstract

The effects of quaternary N-methylated nicotine derivatives were examined on invitro uptake of [3H]dopamine ([3H]DA) in rat striatal slices. Striatal slices were incubated with a 10 μM concentration of the following compounds: N-methylnicotinium, N-methylnornicotinium, N-methylcotininium, N,N′ -dimethylnicotinium and N′ -methylnicotinium salts. The results clearly indicated that significant (60%) inhibition of [3H]DA uptake occurred with those compounds possessing a N-methylpyridinium group; whereas, compounds that were methylated at the N′ -pyrrolidinium position were less effective or exhibited no inhibition of [3H]DA uptake. The results suggest that high concentrations of quaternary N-methylated nicotine metabolites which are structurally related to the neurotoxin MPP+, and which may be formed in the CNS, may protect against Parkinson's Disease and explain the inverse relationship between smoking and Parkinsonism reported in epidemiologic studies.

References (21)

  • H. Sershen et al.

    Eur. J. Pharmacol.

    (1984)
  • T.L. Perry et al.

    Neurosci. Lett.

    (1987)
  • H. Sershen et al.

    Neurosci. Lett.

    (1988)
  • L.A. Carr et al.

    Neuropharmacol.

    (1990)
  • K.C. Cundy et al.

    Biochem. Pharmacol.

    (1985)
  • H. McKennis et al.

    J. Biol. Chem.

    (1963)
  • G.B. Neurath et al.

    J. Chromatogr. Biomed. Applic.

    (1987)
  • P.A. Crooks et al.

    Biochem. Pharmacol.

    (1988)
  • J.A. Baron

    Neurology

    (1986)
  • J.W. Langston et al.

    Science

    (1983)
There are more references available in the full text version of this article.

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