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  • Title: Effect of a nicotine vaccine on nicotine binding to β2*-nicotinic acetylcholine receptors in vivo in human tobacco smokers.
    Author: Esterlis I, Hannestad JO, Perkins E, Bois F, D'Souza DC, Tyndale RF, Seibyl JP, Hatsukami DM, Cosgrove KP, O'Malley SS.
    Journal: Am J Psychiatry; 2013 Apr; 170(4):399-407. PubMed ID: 23429725.
    Abstract:
    OBJECTIVE: Nicotine promotes smoking partly by binding to β2-containing nicotinic acetylcholine receptors (β2*-nAChRs) in the brain. Smoking one tobacco cigarette results in occupation of 80% of β2*-nAChRs for more than 6 hours. This likely contributes to maintenance of smoking dependence and cessation difficulty. Developing nicotine vaccines could improve treatments. The authors used [123I]5-I-A-85380 single photon emission computed tomography (SPECT) to evaluate the effect of 3'-AmNic-rEPA on the amount of nicotine that binds to β2*-nAChRs in smokers' brain cortical and subcortical regions. METHOD: Eleven smokers who smoked an average of 19 cigarettes per day, had smoked for 10 years on average, and met criteria for nicotine dependence were given SPECT scans on two days: before and after immunization with 4-400 μg of 3'-AmNic-rEPA. On scan days, three 30-minute baseline emission scans were followed by intravenous administration of nicotine (1.5 mg/70 kg body weight) and up to nine 30-minute emission scans. RESULTS: β2*-nAChR availability was quantified as VT/fP (total distribution volume divided by free plasma concentration), and nicotine binding was derived by the Lassen plot approach. Immunization led to a 12.5% reduction in nicotine binding. Nicotine bound to β2*-nAChRs correlated positively with nicotine injected before but not after vaccination. The daily number of cigarettes and desire for a cigarette decreased after vaccination. CONCLUSIONS: This proof-of-concept study demonstrates that immunization with nicotine vaccine can reduce the amount of nicotine binding to β2*-nAChRs and disrupt the relationship between administered nicotine and nicotine available to occupy β2*-nAChRs.
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