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

Life Sci. 1992;50(25):PL233-7. doi: 10.1016/0024-3205(92)90533-u.


The effects of quaternary N-methylated nicotine derivatives were examined on in vitro uptake of [3H]dopamine ([3H]DA) in rat striatal slices. Striatal slices were incubated with a 10 microM 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • In Vitro Techniques
  • Male
  • Nicotine / analogs & derivatives
  • Nicotine / chemistry
  • Nicotine / metabolism*
  • Nicotine / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship


  • Nicotine
  • Dopamine