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

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.