Dose-dependent stereoselective activation of the trigeminal sensory system by nicotine in man

Thuerauf, Norbert; Kaegler, M.; Dietz, Rainer; Barocka, Arnd; Kobal, Gerd

doi:10.1007/s002130050885

Cited by 60 publications

(51 citation statements)

References 32 publications

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“…For most participants, this level is around 0.3≤P≤0.7 when it comes to 1-undecanol (Figure 2, right), and around 0.1≤P≤0.5 when it comes to decyl acetate (Figure 4, right channels that includes the vanilloid, menthol, and other pungent compounds receptors is a likely candidate (Voets and Nilius 2003;Voets et al 2005). So is the nicotinic receptor (Thuerauf et al 1999). Chemically reactive VOCs capable of damaging cells can release intracellular nociceptive mediators which, in turn, stimulate endogenous receptors that signal damage to cells (Sutherland et al 2000;Garle and Fry 2003).…”

Section: Discussionmentioning

confidence: 98%

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

et al. 2007

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We measured concentration-detection (i.e., psychometric) functions for the eye irritation evoked by three homologous n-alcohols (1-nonanol, 1-decanol, and 1-undecanol) and two homologous acetates (nonyl and decyl acetate). A vapor delivery device based on a dynamic dilution of stimuli in nitrogen served to present various concentrations of each compound, including the undiluted vapor, to the subjects (n≥26).Delivered concentrations were quantified by gas chromatography. Detection probability (P) was assessed via a three-alternative, forced-choice procedure, and quantified on a scale ranging from P = 0.0 (chance detection) to P = 1.0 (perfect detection). Flowrate to the eye equaled 2.5 L/min and time of exposure was 6 sec. The functions for 1-undecanol and decyl acetate plateau at P ≈ 0.5 and P ≈ 0.25, respectively, such that further increases in concentration failed to increase detection notably. Thus, both series reached a break-point, or cut-off, in detection of ocular irritation. The present outcome provides additional evidence that the cut-off does not rest on the low vapor concentration of the homolog but, more likely, on the homolog exceeding a critical molecular dimension(s) which prevents it from interacting effectively with the appropriate receptors.

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Section: Discussionmentioning

confidence: 98%

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

et al. 2007

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“…3 Nicotine is bitter tasting 4 and can elicit pain and burning in the airways when tobacco smoke is inhaled. 5,6 Aversion to the bitter taste…”

Section: Introductionmentioning

confidence: 99%

Relationships of PROP Taste Phenotype, Taste Receptor Genotype, and Oral Nicotine Replacement Use

Ahijevych

Tepper

Graham

et al. 2014

NICTOB

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Introduction: Recommended dosage of oral nicotine replacement therapy (NRT) product is often not achieved in smoking cessation attempts. n-6-propylthiouracil (PROP) bitter taste phenotype may be a potential risk factor for non-adherence to oral NRT products due to their bitter taste. There is limited literature on this phenotype in the context of smoking and none in relation to oral NRT pharmacotherapy. Methods: The association of PROP taste phenotype with NRT usage and sensory response to products was examined. In a cross-over experimental design, 120 participants received a 1 week supply of nicotine inhalers and 1 week of nicotine lozenges with random assignment to order. Mixed effects linear model analyses were conducted. Results: PROP taste phenotype and taste receptor genotype were not associated with NRT usage or sensory response to NRT, after adjusting for other factors. However, PROP non-tasters used a higher number of lozenges per day (continuous exposure) than nicotine cartridges (intermittent exposure). Unexpectedly, half of baseline PROP non-tasters shifted to taster phenotype 2 weeks after smoking cessation or reduction. Menthol cigarette smokers identified higher NRT strength of sensation scores than nonmenthol smokers. Taste receptor genotype was related to PROP taste phenotype (Kendall τ = .591, p = .0001). Conclusions: A nonsignificant relationship of PROP phenotype and NRT usage may be associated with NRT under-dosing and limited variance in the outcome variable. PROP non-tasters' greater use of lozenges is consistent with nicotine exposure being less aversive to non-tasters. Further research of this and other factors impacting NRT usage are warranted to effectively inform smoking cessation pharmacotherapy.

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“…Nicotine not only represents the main addictive component of smoking but it also greatly contributes to the sensory properties of tobacco (Laviolette and van der Kooy, 2004;Walker et al, 1996;Hummel et al, 1992a, b;Thuerauf et al, 1999Thuerauf et al, , 2000. The substance presented to the nasal cavity at low concentrations evokes 'odorous' sensations and at higher concentrations 'burning' and 'stinging' sensations, possibly mediated by nicotinic acetylcholine receptors (nAchR) (Walker et al, 1996;Thuerauf et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…The substance presented to the nasal cavity at low concentrations evokes 'odorous' sensations and at higher concentrations 'burning' and 'stinging' sensations, possibly mediated by nicotinic acetylcholine receptors (nAchR) (Walker et al, 1996;Thuerauf et al, 1999). In contrast to the majority of other chemical compounds, nicotine activates the olfactory and the trigeminal system at relatively low concentrations (Hummel et al, 1992a, b).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to the majority of other chemical compounds, nicotine activates the olfactory and the trigeminal system at relatively low concentrations (Hummel et al, 1992a, b). During the last decade stereospecific differences between nicotine enantiomers have been reported for the nasal trigeminal sensory system (Thuerauf et al, 1999(Thuerauf et al, , 2000Walker et al, 1996). S-(À)-nicotineFthe natural isomer of tobaccoFpossesses lower trigeminal thresholds and higher stimulus strength for the 'burning' and the 'stinging' sensation compared to R-( þ )-nicotine.…”

Section: Introductionmentioning

confidence: 99%

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The Influence of Mecamylamine on Trigeminal and Olfactory Chemoreception of Nicotine

Thuerauf

Markovic

Braun

et al. 2005

Neuropsychopharmacol

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Nicotine presented to the nasal cavity at low concentrations evokes 'odorous' sensations, and at higher concentrations 'burning' and 'stinging' sensations. A study in smokers and nonsmokers provided evidence of a relationship between the experience with the pharmacological action of S-(À)-nicotine and the perceived pleasantness/unpleasantness following nasal stimulation with S-(À)-nicotine. Mecamylamine, a nicotinic acetylcholine-receptor-(nAch-R) antagonist, was able to block painful responses following chemical stimulation of the human tongue and to block responses from the rat's ethmoidal nerve. The aim of our study in humans was to investigate the effects of mecamylamine on the olfactory and the trigeminal chemoreception of nicotine enantiomers. In order to achieve this aim, we determinedFbefore and after mecamylamineF(1) detection thresholds, trigeminal thresholds, and intensity estimates (stimulus intensity) and (2) recorded the negative mucosal potential (NMP) following nasal stimulation with nicotine in a placebo-controlled double blind study (n ¼ 15). CO 2 was used as a trigeminal and H 2 S as an olfactory control stimulus. Mecamylamine significantly increased trigeminal thresholds of S-(À)-nicotine and reduced intensity estimates and NMPs following stimulation with nicotine enantiomers, whereas mecamylamine did not influence NMPs and trigeminal intensity estimates following stimulation with CO 2 . In contrast, mecamylamine did neither influence detection thresholds nor olfactory intensity estimates following stimulation with olfactory nicotine concentrations. These results demonstrate that the trigeminal nasal chemoreception of nicotine enantiomers, in contrast to CO 2 , is mediated by nAch-Receptors and give evidence that the olfactory chemoreception of nicotine is independent from peripheral nAchReceptors.

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Dose-dependent stereoselective activation of the trigeminal sensory system by nicotine in man

Abstract: Our results clearly demonstrate the different stereoselective activation of the trigeminal sensory system by R(+)-and S(-)-nicotine, indicating the presence of specific stereoselective receptors on trigeminal nociceptive Adelta- and C-fibers.

Cited by 60 publications

References 32 publications

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

Relationships of PROP Taste Phenotype, Taste Receptor Genotype, and Oral Nicotine Replacement Use

The Influence of Mecamylamine on Trigeminal and Olfactory Chemoreception of Nicotine

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