ArticleNicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco2014
Pharmacokinetic and pharmacodynamics studies of nicotine after oral administration in mice: effects of methoxsalen, a CYP2A5/6 inhibitor.
Article in Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Effect of nicotine on L-dopa-induced dyskinesia in animal models of Parkinson's disease: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2014Pooled it
- Effect of nicotine on the energy metabolism of substantia nigra cells in MPTP-induced Parkinson's disease.Iranian journal of basic medical sciences · 2025Article
- The Role of Nicotine Metabolic Rate on Nicotine Dependence and Rewarding: Nicotine Metabolism in Chinese Male Smokers and Male Mice.Molecular neurobiology · 2024Article
- Methoxsalen Inhibits the Acquisition of Nicotine Self-Administration: Attenuation by Cotinine Replacement in Male Rats.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- Nicotine rebalances NADNature communications · 2023Article
- Pharmacokinetic and pharmacodynamic studies of nicotine in rat brain: a simultaneous investigation of nicotine metabolites and the release of neurotransmittersFrontiers in chemistry · 2023Article
- Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease.Frontiers in pharmacology · 2023Article
- Advances in smoking cessation pharmacotherapy: Non-nicotinic approaches in animal models.Neuropharmacology · 2020Review
- The Novel CYP2A6 Inhibitor, DLCI-1, Decreases Nicotine Self-Administration in Mice.The Journal of pharmacology and experimental therapeutics · 2020Article
- Dynamic changes in lung responses after single and repeated exposures to cigarette smoke in mice.PloS one · 2019Article
- A convenient UHPLC-MS/MS method for routine monitoring of plasma and brain levels of nicotine and cotinine as a tool to validate newly developed preclinical smoking model in mouse.BMC neuroscience · 2017Article
- Innovative approaches to support smoking cessation for individuals with mental illness and co-occurring substance use disorders.Expert review of respiratory medicine · 2017Review
- The nicotine + alcohol interoceptive drug state: contribution of the components and effects of varenicline in rats.Psychopharmacology · 2016Article
- An Inventory of Methods for the Assessment of Additive Increased Addictiveness of Tobacco Products.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2016Review
- In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone.Psychopharmacology · 2016Article
- Effects of methoxsalen, a CYP2A5/6 inhibitor, on nicotine dependence behaviors in mice.Neuropharmacology · 2014Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
introductionThe use of novel oral nicotine delivery devices and compositions for human consumption and for animal research studies has been increasing in the last several years.
methodsStudies were undertaken to examine whether the systemic administration of methoxsalen, an inhibitor of human CYP2A6 and mouse CYP2A5, would modulate nicotine pharmacokinetics and pharmacological effects (antinociception in the tail-flick, and hot-plate tests, and hypothermia) in male ICR mouse after acute oral nicotine administration.
resultsAdministration of intra peritoneal (ip) methoxsalen significantly increased nicotine's Cmax, prolonged the plasma half-life (fourfold decrease) of nicotine, and increased its area under the curve (AUC) compared with ip vehicle treatment. Methoxsalen pretreatment prolonged the duration of nicotine-induced antinociception and hypothermia (15mg/kg, po) for periods up to 6- and 24-hr postnicotine administration, respectively. Additionally, methoxsalen potentiated nicotine-induced antinociception and hypothermia as evidenced by leftward shifts in nicotine's dose-response curve. Furthermore, this prolongation of nicotine's effects after methoxsalen was associated with a parallel prolongation of nicotine plasma levels in mice. These data strongly suggest that variation in the rates of nicotine metabolic inactivation substantially alter pharmacological effects of nicotine given orally.
conclusionWe have shown that the pharmacological effects of inhibiting nicotine's metabolism after oral administration in mice are profound. Our results suggest that inhibiting nicotine metabolism can be used to dramatically enhance nicotine's bioavailability and its resulting pharmacology, which further supports this inhibitory approach for clinical development of an oral nicotine replacement therapy.
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