Nicotine is more efficient than cotinine at passing the blood-brain barrier in rats.

1. Nicotine and its main metabolite, cotinine, were reported to have distinct behavioral activities in mammals. 2. In this study, cotinine was synthesized without detectable nicotine contamination to compare the ability of nicotine and cotinine to pass the blood-brain barrier (BBB) in rats. 3. The alkaloids were extracted from plasma and brain tissues by methanol, identified by thin-layer chromatography, and quantified by high-pressure liquid chromatography and radioimmunoassays. 4. Consistently, the three methods showed that the passage of cotinine was time, route of administration, and dose dependent and that nicotine was more efficient than cotinine to pass the BBB. 5. The results suggest that these alkaloids may have central activities that probably result from their actions at distinct molecular levels.