A COMPARISON OF THE BINDING OF NICOTINE AND NONNICOTINE STEREOISOMERS TO NICOTINIC BINDING-SITES IN RAT-BRAIN CORTEX

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