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摘要
The primary objective of this project was to determine the alpha 4 beta 2* nicotinic acetylcholine receptor (nAChR) occupancy in human brain of a single low dose of varenicline (0.5 mg), and to explore the relationship between receptor occupancy by varenicline and tobacco withdrawal symptoms (*denoting other putative nAChR subunits). Otherwise healthy smokers (n = 9) underwent two positron emission tomography (PET) sessions with the selective alpha 4 beta 2* radioligand 2-FA. For the PET sessions, participants received either a low dose of varenicline (0.5 mg) or matching placebo pill (double-blind, random order) before imaging. For both sessions, participants received bolus plus continuous infusions of 2-FA, were scanned for 1 h after allowing the radiotracer to reach a steady state, smoked to satiety, and were scanned for 2 more hours. We estimated the fractional receptor occupancy by a single dose of varenicline (0.5 mg) and the corresponding varenicline dissociation constant (K-V), along with the effect of low-dose varenicline, pill placebo, and smoking-to-satiety on withdrawal rating scales. The data are compatible with 100% occupancy of alpha 4 beta 2* nAChRs by a single dose of varenicline, with a 90% lower confidence limit of 89% occupancy for the thalamus and brainstem. The corresponding 90% upper limit on effective K-V with respect to plasma varenicline was 0.49 nM. Smoking to satiety, but not low-dose varenicline, significantly reduced withdrawal symptoms. Our findings demonstrate that low-dose varenicline results in saturation of alpha 4 beta 2* nAChRs in the thalamus and brainstem without reducing withdrawal symptoms. Neuropsychopharmacology (2012) 37, 1738-1748; doi:10.1038/npp.2012.20; published online 7 March 2012
- 出版日期2012-6
