The Nicotrol® (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 (β2*-nAChRs). Previous studies examined β2*-nAChR occupancy after administration of regular and low-
nicotine cigarettes. Here, we measured occupancy of β2*-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 [123I]5-IA-85380 SPECT studies with either a
nicotine inhaler (n=9) or tobacco cigarette (n=4) challenge. [123I]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 β2*-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 β2*-nAChRs by
nicotine after use of the
inhaler vs. a cigarette and confirm the ability of the
nicotine inhaler to relieve
withdrawal symptoms.