PHARMACOLOGIC MECHANISMS AND TREATMENT OF NICOTINE DEPENDENCE

尼古丁依赖的普遍存在，随之而来的健康问题，以及使用者在保持戒断方面的困难，使其成为我们社会中最有问题的滥用药物之一。临床研究的目的是更好地了解尼古丁依赖的病理生理和机制，并有助于开发新的戒烟治疗方法。已经开发了几种尼古丁输送系统来帮助戒烟。其中两种，尼古丁polacrilex和尼古丁透皮贴片，已被批准用于非处方销售。目前，针对戒烟适应症开发的新型尼古丁输送系统，包括尼古丁鼻喷雾剂和尼古丁蒸发器吸入器，作为处方产品可供使用。值得注意的是，这些系统的交付速度更快，而这一因素与更大的滥用可能性有关。因此，尽管这些系统是作为戒烟的辅助工具开发的，但它们本身也可能被滥用。第一项研究旨在检验不同剂量的尼古丁鼻喷雾剂和蒸汽吸入器对生理、主观和表现的影响，并将其与作为标准阳性对照的普通香烟进行比较。这项安慰剂对照、双盲、门诊研究将提供有关这些产品滥用责任的必要信息。可替宁，尼古丁的主要代谢物，作为一种治疗烟草戒断的效果进行了评估。这项研究是基于最近的发现，可替宁引起的主观改变，戒烟的人类吸烟者。本研究的目的是描述可替宁对周期性戒烟吸烟者的药效学影响，包括烟草戒断症状、情绪和主观状态、药物效应、表现和内分泌影响。在门诊协议研究了一种新的治疗烟草戒断的药效学和药代动力学效果。我们发现，用玉米糖浆溶液处理香烟可以显著减少尼古丁和一氧化碳的暴露。此外，这种效果在男性和女性身上是相似的。尼古丁的药代动力学效应在男性和女性中是相似的，这表明吸烟和戒烟模式的性别差异不是由于男性和女性尼古丁代谢的动力学差异。在一项正在进行的贝氟沙酮效果研究中，评估了一种可逆的MAO抑制剂用于戒烟治疗。在对脱硝香烟的进一步研究中，正在对香烟进行初步评估。在另一项研究中，脱硝香烟被用于快速吸烟方案。

The prevalence of nicotine dependence, its accompanying health problems, and the difficulty users have in maintaining abstinence combine to make it one of the most problematic abused drugs in our society. Clinical studies were designed to provide a better understanding of the pathophysiology and mechanisms of nicotine dependence as well as to contribute to the development of putative new smoking cessation treatments. Several nicotine delivery systems have been developed to aid in smoking cessation. Two of these, nicotine polacrilex and nicotine transdermal patches, have been approved for over the counter sales for this purpose. Currently new nicotine delivery systems developed for smoking cessation indications, including a nicotine nasal spray and a nicotinevapor inhaler are available as prescription items . These systems are notable for having a more rapid delivery rate, a factor that has been associated with greater potential for abuse. Therefore, although developed as aids for smoking cessation, such systems may be abused in their own right. The first study was designed to examine the physiological, subjective and performance effects of various doses of nicotine nasal spray and vapor inhaler compared to a regular cigarette, which served as a standard positive control. This placebo-controlled, double blind, outpatient study will provide needed information about the abuse liability of these products. The effects of cotinine, the major metabolite of nicotine, was evaluated as a treatment for tobacco withdrawal. This study was based on recent findings that cotinine administration induced subjective changes in abstinent human cigarette smokers. The purpose of the study was to characterize the pharmacodynamic effects of cotinine in cigarette smokers undergoing periodic abstinence, including symptoms of tobacco withdrawal, mood and subjective state, drug effect, performance, and endocrine effects. The pharmacodynamic and pharmacokinetic effects of a new treatment for tobacco withdrawal were studied in an outpatient protocol. We found that treating cigarettes with a corn syrup-based solution significantly reduced exposure to nicotine and CO. Further, the effects were similar in man and women. Pharmacokinetic effects of nicotine were similar in men and women indicating that gender differences in patterns of smoking and tobacco withdrawal are not due to kinetic differences in nicotine metabolism in men and women. In an on-going study the effects of befloxatone, a reversible MAO inhibitor is evaluated for smoking cessation therapy. In further studies of the denicotinized cigarettes, a preliminary evaluation of cigarettes is being conducted. In another study the denicotinized cigarettes are being used in a rapid smoking protocol.