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A comparison of the binding of nicotine and nornicotine stereoisomers to nicotinic binding sites in rat brain cortex

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Summary

Both stereoisomers of nicotine and nornicotine were tested for their ability to competitively displace 3H(-)-nicotine and 3H-acetylcholine (in the presence of atropine), in rat cortex tissue. 3H-acetylcholine was displaced from two binding sites, super-high and high, by (+)-nicotine, (-)-nornicotine and (+)-nornicotine but from a high affinity site by (-)-nicotine. 3H-nicotine was displaced from two sites, high and low affinity by nicotine and nornicotine stereoisomers. The high-affinity 3H(-)-nicotine binding site showed similar binding characteristics to one of the sites labelled by 3H-acetylcholine. IC50 values showed (-)-nicotine to be 13 and 25-fold more potent than (+)-nicotine for displacing 3H-(-)nicotine and 3H-acetylcholine, respectively, but no difference was observed for nornicotine stereoisomers. While (-)-nicotine preferentially bound to the high affinity site of 3H-(-)-nicotine (+)-nicotine preferred the low affinity site. The study provides further evidence for multiple nicotine receptors in brain.

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Authors and Affiliations

  1. Department of Pharmacology, Uppsala University, S-75124, P.O.Box 591, Uppsala, Sweden

    J. R. Copeland, A. Adem & A. Nordberg

  2. Division of Clinical Pharmacology and Therapeutics, Department of Medicine, San Francisco General Hospital, San Francisco, CA, USA

    P. Jacob III

Authors
  1. J. R. Copeland
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  2. A. Adem
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  3. P. Jacob III
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  4. A. Nordberg
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Copeland, J.R., Adem, A., Jacob, P. et al. A comparison of the binding of nicotine and nornicotine stereoisomers to nicotinic binding sites in rat brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 343, 123–127 (1991). https://doi.org/10.1007/BF00168598

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  • DOI: https://doi.org/10.1007/BF00168598

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