New Insights into the Mechanisms of Action of Cotinine and its Distinctive Effects from Nicotine

@article{Grizzell2014NewII,
  title={New Insights into the Mechanisms of Action of Cotinine and its Distinctive Effects from Nicotine},
  author={J. Alex Grizzell and Valentina Echeverria},
  journal={Neurochemical Research},
  year={2014},
  volume={40},
  pages={2032-2046}
}
Abstract Tobacco consumption is far higher among a number of psychiatric and neurological diseases, supporting the notion that some component(s) of tobacco may underlie the oft-reported reduction in associated symptoms during tobacco use. Popular dogma holds that this component is nicotine. However, increasing evidence support theories that cotinine, the main metabolite of nicotine, may underlie at least some of nicotine’s actions in the nervous system, apart from its adverse cardiovascular and… 

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References

SHOWING 1-10 OF 216 REFERENCES
Cotinine, a neuroactive metabolite of nicotine: potential for treating disorders of impaired cognition.
TLDR
Based on its relative safety in man, cotinine should prove useful in the treatment of diseases of impaired cognition and behavior without exhibiting the toxicity usually attributed to nicotine.
The potential role of cotinine in the cognitive and neuroprotective actions of nicotine.
Cotinine: Beyond that Expected, More than a Biomarker of Tobacco Consumption
TLDR
New evidence suggests that the pharmacological and behavioral effects of cotinine may play a key role in promoting tobacco smoking in individuals that suffer from psychiatric conditions and represents a new potential therapeutic agent against psychiatric conditions such as AD and PTSD.
Cotinine: A Potential New Therapeutic Agent against Alzheimer's disease
TLDR
Evidence is discussed showing that cotinine, the main metabolite of nicotine, has many of the beneficial effects but none of the negative side‐effects of its precursor, which indicates it may represent a new therapeutic agent against Alzheimer's disease.
Nicotine and smoking: a perspective from animal studies
  • P. Clarke
  • Psychology, Biology
    Psychopharmacology
  • 2004
TLDR
Clinical evidence suggests that smoking cessation would be facilitated by the administration of a Nicotinic antagonist having a selective action on central nicotinic cholinoceptors of the C6 (ganglionic) type, and Pharmacological studies in animals indicate that such a drug is a reasonable prospect.
Chronologically overlapping occurrences of nicotine-induced anxiety- and depression-related behavioral symptoms: effects of anxiolytic and cannabinoid drugs
  • T. Hayase
  • Psychology, Biology
    BMC Neuroscience
  • 2007
TLDR
The present results support the presence of a chronological overlap of NC-induced anxiety- and depression-related behavioral symptoms, and the contribution of brain CB receptors to these behavioral symptoms.
Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis.
Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior.
TLDR
This Symposium covered a wide area of nicotine studies: genetic, genomic, and functional aspects of nicotinic ACh receptors were studied, as related to anthelmintics and insecticides; interactions between ethanol and nicotine out the ACh receptor were analyzed, in an attempt to explain the well-known heavy drinker-heavy smoker correlation.
Metabolism and Disposition Kinetics of Nicotine
TLDR
Current knowledge about the metabolism and disposition kinetics of nicotine, some other naturally occurring tobacco alkaloids, and nicotine analogs that are under development as potential therapeutic agents are reviewed.
...
1
2
3
4
5
...