Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler
Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler
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DOI：
10.1017/s1461145710001227
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发表时间：
2011-04-01
影响因子：
4.8
通讯作者：
Cosgrove, Kelly P.
中科院分区：
文献类型：
--
作者：
Esterlis, Irina;Mitsis, Effie M.;Cosgrove, Kelly P.
Nicotrol（R）（Pfizer，USA）尼古丁吸入器通过模仿香烟的行为成分并递送受控剂量的尼古丁来减少烟瘾，尼古丁与含有β 2亚基的烟碱乙酰胆碱受体（β（2）*-nAChR）结合。先前的研究检查了在给予常规和低尼古丁香烟后的β（2）*-nAChR占用。在这里，我们测量了通过吸入器给予尼古丁后β（2）*-nAChRs的占用率，以及占用率与吸烟渴望和戒断症状变化之间的关系。吸烟者参加了使用尼古丁吸入器（n=9）或香烟（n=4）激发的[I-123]5-IA-85380 SPECT研究。[I-123]5-IA以推注加恒定输注的方式给药。达到平衡后，收集三个30分钟的基线扫描，受试者使用尼古丁吸入器或普通香烟，并获得多达六个额外的扫描。基于Lassen图法测定受体占有率。在激发前和激发后评价吸烟渴望和戒断症状。使用尼古丁吸入器在激发后2-5小时产生平均55.9+/-6.4%的β（2）*-nAChRs占用率，而使用香烟产生显著更高的受体占用率（F=10.6，p=0.009），在激发后1.5-5小时平均67.6+/-14.1%占用率。尼古丁吸入器使用后戒断症状显著减少（F=6.13，p=0.04）。这些结果表明，使用吸入器与香烟后尼古丁对β（2）*-nAChR的占用率存在显著差异，并证实尼古丁吸入器缓解戒断症状的能力。
The Nicotrol (R) (Pfizer, USA) nicotine inhaler reduces craving by mimicking the behavioural component of cigarettes and delivering controlled doses of nicotine, which binds to the beta-2 subunit-containing nicotinic acetylcholine receptors (beta(2)*-nAChRs). Previous studies examined beta(2)*-nAChR occupancy after administration of regular and low-nicotine cigarettes. Here, we measured occupancy of beta(2)*-nAChRs after administration of nicotine via inhaler, and the relationship between occupancy and changes in craving for tobacco smoking and withdrawal symptoms. Tobacco smokers participated in [I-123]5-IA-85380 SPECT studies with either a nicotine inhaler (n=9) or tobacco cigarette (n=4) challenge. [I-123]5-IA was administered as a bolus plus constant infusion. After equilibrium was achieved, three 30-min baseline scans were collected, and subjects either used the nicotine inhaler or a regular cigarette, and up to six additional scans were obtained. Receptor occupancy was determined based on the Lassen plot method. Craving for tobacco smoking and withdrawal symptoms were evaluated pre- and post-challenge. Use of the nicotine inhaler produced an average 55.9+/-6.4% occupancy of beta(2)*-nAChRs 2-5 h post-challenge, whereas use of a cigarette produced significantly higher receptor occupancy (F=10.6, p=0.009) with an average 67.6+/-14.1% occupancy 1.5-5 h post-challenge. There was a significant decrease in withdrawal symptoms post-nicotine inhaler use (F=6.13, p=0.04). These results demonstrate significant differences in occupancy of beta(2)*-nAChRs by nicotine after use of the inhaler vs. a cigarette and confirm the ability of the nicotine inhaler to relieve withdrawal symptoms.