+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Metabolites of nicotine in rat brain after peripheral nicotine administration. Cotinine, nornicotine, and norcotinine



Metabolites of nicotine in rat brain after peripheral nicotine administration. Cotinine, nornicotine, and norcotinine



Drug Metabolism and Disposition: the Biological Fate of Chemicals 25(1): 47-54



The time course of nicotine metabolite appearance in brain from 5 min-18 hr after subcutaneous administration of S-(-)-[3H-N-methyl]nicotine was determined. Results demonstrated that metabolite appearance in brain was greatest at 4 hr postadministration, whereas levels of nicotine were greatly diminished at this time point. For determination of N-demethylated metabolites, (+/-)-[2'-14C]nicotine was administered subcutaneously to rats, and the presence of nicotine and nicotine metabolites in brain supernatant was determined 4 hr postadministration. Using high-performance liquid radiochromatographic analysis, nicotine and three nicotine metabolites (cotinine, nornicotine, and norcotinine) were identified in brain, together with a fourth minor, unidentified metabolite. After subcutaneous administration of S-(-)-[G-3H]cotinine, significant amounts of cotinine were found in brain over an 18-hr postadministration period; however, no cotinine metabolites were detected. Therefore, cotinine is able to pass the blood-brain barrier and access the central nervous system, but is not biotransformed in brain. Thus, this is the first report of norcotinine as a central nervous system nicotine metabolite. Data indicate that norcotinine detected in brain after peripheral nicotine administration most likely originates from 5'-C-oxidation of brain nornicotine, rather than from N-demethylation of cotinine, as occurs peripherally. Because peripheral biotransformation of nicotine to nornicotine is a minor pathway, the relatively high levels of nornicotine found in brain after peripheral nicotine administration suggest that nornicotine is formed via oxidative N-demethylation of nicotine locally in brain. Nornicotine is pharmacologically active; thus, its presence in brain after peripheral nicotine administration indicates that nornicotine may contribute to the neuropharmacological effects of nicotine and tobacco use.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 009014349

Download citation: RISBibTeXText

PMID: 9010629


Related references

Determination of nicotine metabolites in rat brain after peripheral radiolabeled nicotine administration: detection of nornicotine. Drug Metabolism and Disposition: the Biological Fate of Chemicals 23(10): 1175-1177, 1995

Quantification of nicotine, cotinine, trans-3'-hydroxycotinine, nornicotine and norcotinine in human meconium by liquid chromatography/tandem mass spectrometry. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 863(1): 107-114, 2008

Accumulation of nicotine and its metabolites in rat brain after intermittent or continuous peripheral administration of [2'-(14)C]nicotine. Drug Metabolism and Disposition: the Biological Fate of Chemicals 29(5): 645-651, 2001

Accumulation of nicotine and its metabolites in rat brain after intermittent or continuous peripheral administration of (2'-14C)nicotine. Drug Metabolism and Disposition 29(5): 645-651, 2001

Residence times and half-lives of nicotine metabolites in rat brain after acute peripheral administration of [2'-(14)C]nicotine. Drug Metabolism and Disposition: the Biological Fate of Chemicals 27(12): 1448-1455, 1999

Residence times and half-lives of nicotine metabolites in rat brain after acute peripheral administration of (2'-14C)nicotine. Drug Metabolism and Disposition 27(12): 1448-1455, 1999

Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine: effects of route and ethanol coadministration. Psychopharmacology 232(3): 551-560, 2015

The competition of (-)-[3H]nicotine binding by the enantiomers of nicotine, nornicotine and anatoxin-a in membranes and solubilized preparations of different brain regions of rat. Naunyn-Schmiedeberg's Archives of Pharmacology 348(1): 28-34, 1993

A comparison of nicotine dose estimates in smokers between filter analysis, salivary cotinine, and urinary excretion of nicotine metabolites. Psychopharmacology 189(3): 345-354, 2006

Adolescent nicotine administration changes the responses to nicotine given subsequently in adulthood: adenylyl cyclase cell signaling in brain regions during nicotine administration and withdrawal, and lasting effects. Brain Research Bulletin 76(5): 522-530, 2008

Simultaneous determination of nicotine, cotinine and five additional nicotine metabolites in the urine of smokers using pre-column derivatisation and high-performance liquid chromatography. Journal of Chromatography 419: 375-380, 1987

Plasma nicotine and cotinine levels following intravenous nicotine self-administration in rats. Psychopharmacology 143(3): 318-321, April 11, 1999

Plasma nicotine and cotinine concentrations in mice after chronic oral nicotine administration and challenge doses. European Journal of Pharmaceutical Sciences 1(1): 13-18, 1993

Nicotine and its metabolites. Radioimmunoassays for nicotine and cotinine. Biochemistry 12(24): 5025-5030, 1973

Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems. Journal of Analytical Toxicology 21(4): 310-313, 1997