Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler.

Abstract

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.

• Authors: Irina Esterlis, Effie M Mitsis, Jeffery C Batis, Frederic Bois, Marina R Picciotto, Stephanie M Stiklus, Tracy Kloczynski, Edward Perry, John P Seibyl, Sherry McKee, Julie K Staley, Kelly P Cosgrove
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 14 Issue 3 Pg. 389-98 (Apr 2011) ISSN: 1469-5111 [Electronic] England
• PMID: 21029513 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Nicotinic Agonists
• Receptors, Nicotinic
• nicotinic receptor beta2
• Nicotine

Topics

• Administration, Inhalation
• Adult
• Behavior, Addictive (drug therapy)
• Female
• Humans
• Male
• Middle Aged
• Nicotine (administration & dosage, blood, pharmacology)
• Nicotinic Agonists (administration & dosage, blood, pharmacology)
• Receptors, Nicotinic (metabolism)
• Smoking
• Smoking Cessation
• Substance Withdrawal Syndrome (drug therapy)
• Young Adult