Anesthetic and synthetic cooling flavors in E-cigarettes: Chemistry and respiratory effects modulating nicotine intake

电子烟中的麻醉剂和合成清凉香料：调节尼古丁摄入量的化学和呼吸效应

• 批准号: 9982329
• 负责人: SVEN-ERIC JORDT
• 金额: $ 47.35万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982329
• 关键词: Adolescent; Advisory Committees; Affect; Afferent Neurons; Aldehydes; Analgesics; Anesthetics; Blood; Calcium; Cells; Chemicals; Chemistry; Chronic; Cigarette; Cigarette Smoker; Clove; Consumption; Cotinine; Data; Dental; Detection; Electronic cigarette; Epidemiology; Eugenol; Family; Family Smoking Prevention and Tobacco Control Act; Flavoring; Gas Chromatography; High School Student; Human; Human Cloning; Image; Industry; Inhalation; Intake; Ion Channel; Ions; Irritants; Liquid substance; Mass Fragmentography; Mass Spectrum Analysis; Measures; Mediating; Menthol; Methods; Microscopic; Modeling; Motion; Mus; Nerve; Neurons; Nicotine; Perception; Pharmacology; Physiological; Plethysmography; Powder dose form; Property; Reader; Rodent; Sensory; Sensory Nerve Endings; Smoker; Sodium; Stimulus; System; TRPV1 gene; Tobacco; Tobacco use; Trigeminal System; Vendor; Youth; addiction; base; cold temperature; cryogenics; design; e-cigarette aerosols; electronic cigarette use; electronic liquid; experimental study; irritation; member; methyl lactate; methyl salicylate; neuronal excitability; novel; ratiometric; receptor; respiratory; response; sensory system; smoking cessation; somatosensory; tobacco products; vaping; vapor; ventilation

SUMMARY The Family Smoking Prevention and Tobacco Control Act (FSPTCA) prohibits the addition of artificial or natural flavors to tobacco cigarettes, with the exception of menthol. While the prohibition of flavored cigarettes in 2009 set in motion a significant decline in youth tobacco use, the proportion of menthol cigarette smokers has increased, suggesting that menthol may promote initation and maintain addiction. Flavor perception results from a synthesis of stimuli carried by gustatory, olfactory and somatosensory nerves. Cooling flavors such as menthol are considered soothing,. TRPM8, a member of the TRP ion channel family, is the target of menthol and other cooling agents in cold-sensing neurons and is also activated by cold temperature. The flavor industry has developed a range of synthetic cooling agents with novel sensory properties. These synthetic cooling agents have been detected in unregulated electronic cigarette liquids and are sold by online vendors as powders or solutions to mix into E-liquids.Other flavorants may also affect properties of sensory systems, including clove flavors, flavored with eugenol, a widely used dental anesthetic, and wintergreen flavors, flavored with methyl salicylate, a topical analgesic. In our preliminary studies we show that synthetic coolants and eugenol strongly activate TRPM8 channels. We performed a chemical analysis of clove-flavored E-liquids, and revealed that some contain very high eugenol levels (>100mM). In mice we observed that menthol reduced respiratory irritation by aldehyde-flavorant containing E-liquids, suggesting that menthol facilitates inhalation. We also observed that menthol increased cotinine levels, suggesting higher nicotine intake. Based on these findings, we hypothesize that some electronic cigarette liquids contain pharmacologically active flavorants that produce vapors with counterirritant or anesthetic effects suppressing respiratory irritation and facilitating initiation of product use. The following specific aims, using analytical chemical, pharmacological and physiological methods, are designed to produce evidence for or against this hypothesis. Aim 1: Determine contents of anesthetic and cooling agents in E-cigarette liquids and condensed vapors Aim 2: Determine pharmacological effects of E-liquids and condensed vapors containing anesthetic or cooling agents on mouse and human irritant receptors and excitability of trigeminal sensory neurons Aim 3: Measure impact of vapor exposure on ventilation and the respiratory irritation response in mice. Due to the close similarities between human and rodent TRP ion channels and their flavorant pharmacology, data resulting from these studies may support efforts to regulate some flavorants as pharmacologically active agents.

总结 《家庭吸烟预防和烟草控制法》（FSPTCA）禁止添加人工或天然的烟草。 烟草的香味，除了薄荷醇。虽然2009年禁止加香香烟 在运动中的青年烟草使用显着下降，薄荷香烟吸烟者的比例， 增加，表明薄荷醇可能促进启动和维持成瘾。 味觉、嗅觉和躯体感觉神经所携带的刺激综合而成。 清凉的味道，如薄荷醇被认为是舒缓的。TRPM8是TRP离子通道家族的成员， 薄荷醇和其他冷却剂在冷感觉神经元中的靶点，也被冷温度激活。 香料工业已经开发出一系列具有新颖感官特性的合成清凉剂。这些 在不受管制的电子烟液体中检测到合成冷却剂， 供应商作为粉末或溶液混合到电子液体中。其他调味剂也可能影响感官特性， 系统，包括丁香香料，用丁香酚调味，一种广泛使用的牙科麻醉剂，和冬青香料， 用水杨酸甲酯调味一种局部止痛剂在我们的初步研究中，我们表明合成冷却剂 和丁香酚强烈激活TRPM8通道。我们对丁香味的电子烟油进行了化学分析 并揭示了一些含有非常高的丁香酚水平（>100mM）。在小鼠中，我们观察到， 含有薄荷香料的电子液体的呼吸道刺激，表明薄荷醇有助于吸入。 我们还观察到薄荷醇增加了可替宁水平，表明尼古丁摄入量较高。 基于这些发现，我们假设一些电子烟液体含有抗氧化剂， 产生具有抑制呼吸道刺激的反刺激或麻醉作用的蒸汽的调味剂， 促进产品使用的开始。以下具体目标，使用分析化学，药理学和 生理学方法，旨在产生支持或反对这一假设的证据。 目的1：测定电子烟液体和冷凝蒸汽中麻醉剂和冷却剂的含量 目的2：确定含有麻醉剂或冷却剂的电子液体和冷凝蒸汽的药理作用 药物对小鼠和人类刺激性受体和三叉神经感觉神经元兴奋性的影响 目的3：测定蒸气暴露对小鼠通气功能和呼吸道刺激反应的影响。 由于人类和啮齿动物TRP离子通道及其香料药理学之间的密切相似性， 从这些研究中得到的数据可以支持将某些调味剂作为调味剂来调节的努力 剂.

项目成果

Tobacco industry's investment in sweetness comes full circle.

烟草业对甜味的投资圆满结束。

• DOI: 10.1136/bmj.l2338
• 发表时间: 2019
• 期刊: BMJ (Clinical research ed.)
• 作者: Jordt,Sven-Eric;Jabba,Sairam
• 通讯作者: Jabba,Sairam

Ice flavours and non-menthol synthetic cooling agents in e-cigarette products: a review.

电子烟产品中的冰口味和非胸膜合成冷却剂：评论。

• DOI: 10.1136/tobaccocontrol-2021-057073
• 发表时间: 2023-11
• 期刊: TOBACCO CONTROL
• 影响因子: 5.2
• 作者: Leventhal, Adam M.;Tackett, Alayna P.;Whitted, Lauren;Jordt, Sven Eric;Jabba, Sairam, V
• 通讯作者: Jabba, Sairam, V

Sweeteners are added to modify consumer behaviour.

添加甜味剂是为了改变消费者的行为。

• DOI: 10.1136/bmj.l366
• 发表时间: 2019
• 期刊: BMJ (Clinical research ed.)
• 作者: Jordt,SvenE;Jabba,Sairam
• 通讯作者: Jabba,Sairam

Chemical Adducts of Reactive Flavor Aldehydes Formed in E-Cigarette Liquids Are Cytotoxic and Inhibit Mitochondrial Function in Respiratory Epithelial Cells.

• DOI: 10.1093/ntr/ntaa185
• 发表时间: 2020-12-15
• 期刊: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
• 作者: Jabba SV;Diaz AN;Erythropel HC;Zimmerman JB;Jordt SE
• 通讯作者: Jordt SE

Differences in flavourant levels and synthetic coolant use between USA, EU and Canadian Juul products.

• DOI: 10.1136/tobaccocontrol-2019-055500
• 发表时间: 2020-04-27
• 期刊: Tobacco control
• 影响因子: 5.2
• 作者: Erythropel HC;Anastas PT;Krishnan-Sarin S;O'Malley SS;Jordt SE;Zimmerman JB
• 通讯作者: Zimmerman JB