Safety of Cotinine in Humans: Physiologic, Subjective, and Cognitive Effects

@article{Hatsukami1997SafetyOC,
  title={Safety of Cotinine in Humans: Physiologic, Subjective, and Cognitive Effects},
  author={Dorothy K. Hatsukami and M Grillo and Paul R. Pentel and Cheryl Oncken and Robin L. Bliss},
  journal={Pharmacology Biochemistry and Behavior},
  year={1997},
  volume={57},
  pages={643-650}
}
Preliminary data suggest that cotinine, the major metabolite of nicotine, may be behaviorally active. Studies involving the administration of cotinine at doses that produce high blood concentrations (in excess of those produced by cigarette smoking) may be of interest. This inpatient, 10-day human study examined the safety and the effects from several high doses of oral cotinine fumarate (40, 80, or 160 mg) or placebo in abstinent cigarette smokers. All subjects smoked cigarettes ad lib during… Expand
Effects of cotinine on cigarette self-administration
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Cotinine appears potentially to have a selective modulatory effect on nicotine withdrawal symptoms but not on cigarette smoking. Expand
Cotinine: effects with and without nicotine
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Cotinine appears to antagonize the effects of nicotine in the alleviation of withdrawal symptoms at concentrations higher than that attained from normal smoking, which does not appear to be mediated by changes in nicotine disposition. Expand
Lack of effect of 5HT3 antagonist in mediating subjective and behavioral responses to cotinine
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There was a near but nonsignificant difference among groups on a measure of tobacco withdrawal and no significant differences on global measures of drug effects or physiological measures, which do not strongly support the hypothesis that 5HT(3) agonism is the mechanism by which cotinine offsets the effects of nicotine. Expand
Cotinine, a neuroactive metabolite of nicotine: potential for treating disorders of impaired cognition.
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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. Expand
The potential role of cotinine in the cognitive and neuroprotective actions of nicotine.
TLDR
New appreciation for the role of cotinine in nicotine's actions, and as a pharmacological agent in its own right, particularly in aspects of cognitive function and for neuroprotection, ultimately may be applied towards the treatment of Alzheimer's disease and related disorders, and for various psychiatric syndromes. Expand
Clinical pharmacology of oral cotinine.
TLDR
It is concluded that administration of oral cotinine with measurement in saliva samples is easy, safe, and provides an accurate estimate of systemic clearance and half-life of cotinines. Expand
Effects of high dose transdermal nicotine replacement in cigarette smokers
TLDR
The present results suggest that the use of high dose NRT is safe, leads to significant reductions in smoking, significant but less reductions in total NNAL and carbon monoxide due to compensatory smoking. Expand
New Insights into the Mechanisms of Action of Cotinine and its Distinctive Effects from Nicotine
TLDR
The effects of cotinine are reviewed, including comparisons with nicotine, and potential mechanisms of c nicotine-specific actions in the central nervous system which are, to date, still being elucidated are discussed. Expand
Disconnection between activation and desensitization of autonomic nicotinic receptors by nicotine and cotinine
TLDR
The results illustrate the disconnection between nicotinic receptor activation and receptor desensitization, and they suggest that cotinine's pharmacological actions are either mediated through partial desensItization, or through non-ganglionic subtypes of Nicotinic receptors. Expand
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. Expand
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References

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Pharmacodynamic effects of cotinine in abstinent cigarette smokers
TLDR
It is indicated that cotinine is behaviorally active in the setting of cigarette abstinence at blood concentrations similar to those commonly achieved through daily cigarette smoking. Expand
Nicotine dependence in rats.
TLDR
The utility of sensitive behavioral tests to reveal effects of nicotine abstinence is illustrated, as there was a marked suppression in behavior reinforced by the sweetened solution, and this disruption was immediately reversed when nicotine was reinstated. Expand
Cotinine disposition and effects
TLDR
It is concluded that, at levels to which cigarette smokers are generally exposed, cotinine exerts no cardiovascular activity and weak, if any, psychologic activity. Expand
Studies on the respiratory and cardiovascular effects of (-)-cotinine.
TLDR
It has been shown that (-)-cotinine has a depressor activity which was not abolished by ordinary blocking doses of atropine or diphenhydramine, and the presence of depressorActivity in the decerebrate and spinal dog is consistent with the suggestion that the effect may be mediated through the ability of (-)- Cotinine to produce, directly or indirectly, a vascular muscular relaxation. Expand
Pharmacokinetics of nicotine, cotinine, and 3'-hydroxycotinine in cigarette smokers.
TLDR
The high percentage of renal clearance suggests that further metabolization of this compound is limited, and no evidence for a mutagenic activity of 3'-hydroxycotinine or of urine extracts from subjects dosed with hydroxycotinines was found with the S. typhimurium microsome assay. Expand
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TLDR
Observer and subject ratings of the DSM-III symptoms of craving for tobacco, irritability, anxiety, difficulty concentrating, and restlessness increased after cessation, and bradycardia, impatience, somatic complaints, insomnia, increased hunger, and increased eating occurred after cessation. Expand
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TLDR
The experiments indicate the metabolites of nicotine and cocaine are behaviorally active and may contribute to the pharmacological profile of the parent compounds. Expand
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TLDR
The results showed that there were no significant withdrawal effects on the measures at 2, 4, and 8 hours after cigarette deprivation with the exception of poorer performance on the Trail Making Test (B) at 4 hours, However, there weresignificant withdrawal effects at 24-hours deprivation. Expand
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TLDR
Objective data indicate that after tobacco deprivation smokers actually sleep longer, which contradicts subjective reports of insomnia, and is believed to be the first to simultaneously measure changes in caloric intake, fluid retention, and physical activity after Tobacco deprivation. Expand
N-Methylation of nicotine ad cotinine in vivo.
TLDR
The present report describes the isolation and identification of the methonium compounds formed by the biological methylation of the pyridine rings of (-)-nicotine and ( -)-cotinine in oivo. Expand
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