Nicotine is more efficient than cotinine at passing the blood-brain barrier in rats
- PMID: 9590561
- PMCID: PMC11560172
- DOI: 10.1023/a:1022501131709
Nicotine is more efficient than cotinine at passing the blood-brain barrier in rats
Abstract
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.
Similar articles
-
Simultaneous determination of nicotine and its metabolite, cotinine, in rat blood and brain tissue using microdialysis coupled with liquid chromatography: pharmacokinetic application.J Chromatogr A. 2005 Sep 23;1088(1-2):152-7. doi: 10.1016/j.chroma.2005.01.042. J Chromatogr A. 2005. PMID: 16130745
-
Accumulation of nicotine and its metabolites in rat brain after intermittent or continuous peripheral administration of [2'-(14)C]nicotine.Drug Metab Dispos. 2001 May;29(5):645-51. Drug Metab Dispos. 2001. PMID: 11302929
-
Brain uptake kinetics of nicotine and cotinine after chronic nicotine exposure.J Pharmacol Exp Ther. 2005 Aug;314(2):636-42. doi: 10.1124/jpet.105.085381. Epub 2005 Apr 21. J Pharmacol Exp Ther. 2005. PMID: 15845856
-
Electron-impact and chemical ionization detection of nicotine and cotinine by gas chromatography-mass spectrometry in rat plasma and brain.J Chromatogr. 1992 Aug 7;579(1):93-8. doi: 10.1016/0378-4347(92)80366-x. J Chromatogr. 1992. PMID: 1447354
-
Pharmacokinetic analysis of nicotine and its metabolites (cotinine and trans-3'-hydroxycotinine) in male Sprague-Dawley rats following nose-only inhalation, oral gavage, and intravenous infusion of nicotine.Toxicol Sci. 2024 Dec 1;202(2):196-209. doi: 10.1093/toxsci/kfae120. Toxicol Sci. 2024. PMID: 39270062
Cited by
-
Cotinine: a potential new therapeutic agent against Alzheimer's disease.CNS Neurosci Ther. 2012 Jul;18(7):517-23. doi: 10.1111/j.1755-5949.2012.00317.x. Epub 2012 Apr 25. CNS Neurosci Ther. 2012. PMID: 22530628 Free PMC article. Review.
-
Cotinine: Beyond that Expected, More than a Biomarker of Tobacco Consumption.Front Pharmacol. 2012 Oct 10;3:173. doi: 10.3389/fphar.2012.00173. eCollection 2012. Front Pharmacol. 2012. PMID: 23087643 Free PMC article.
-
Simultaneous quantification of tobacco alkaloids and major phase I metabolites by LC-MS/MS in human tissue.Int J Legal Med. 2015 Mar;129(2):279-87. doi: 10.1007/s00414-014-1093-y. Epub 2014 Oct 11. Int J Legal Med. 2015. PMID: 25304849
-
The nicotine metabolite, cotinine, alters the assembly and trafficking of a subset of nicotinic acetylcholine receptors.J Biol Chem. 2015 Oct 2;290(40):24403-12. doi: 10.1074/jbc.M115.661827. Epub 2015 Aug 12. J Biol Chem. 2015. PMID: 26269589 Free PMC article.
-
Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine: effects of route and ethanol coadministration.Psychopharmacology (Berl). 2015 Feb;232(3):551-60. doi: 10.1007/s00213-014-3681-4. Epub 2014 Jul 20. Psychopharmacology (Berl). 2015. PMID: 25038869 Free PMC article.
References
-
- Anderson, D. J., and Arneric, S. P. (1994). Nicotinic receptor binding of [3H]nicotine, [3H]cytisine and [3H]methylcarbamylcholine in rat brain. Eur. J. Pharmacol.253:261–267. - PubMed
-
- Andersson, K., Jasson, A., Kuylenstierna, F., and Eneroth, P. (1993). Nicotine and its major metabolite cotinine have different effects on aldosterone and prolactin serum levels in the normal male rat. Eur. J. Pharmacol.228:305–312. - PubMed
-
- Benowitz, N. L., Kuyt, F., Jacob, P., III, Jones, R. T., and Osman, A.-L. (1983). Cotinine disposition and effects. Clin. Pharmacol. Ther.34:604–611. - PubMed
-
- Bowman, E. R., and McKennis, H., Jr. (1963). Cotinine preparation. Biochem. Prep.10:36–39.
-
- Bowman, E. R., Turnbull, L. B., and McKennis, H., Jr. (1959). Metabolism of nicotine in the human and excretion of pyridine compounds by smokers. J. Pharmacol. Exp. Ther.127:92–95. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources