Dataset Information

Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism.

ABSTRACT: The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR (?4?2* subtype) availability using PET imaging of the radiotracer 2-(18)F-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-(18)F-FA-85380, or 2-(18)F-FA).Twenty-four smokers-12 slow metabolizers (NMR < 0.26) and 12 normal metabolizers (NMR ? 0.26)-underwent 2-(18)F-FA-PET brain imaging after overnight nicotine abstinence (18 h before scanning), using a validated bolus-plus-infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest, with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed before and after the scans.Thalamic nAChR ?4?2* availability was significantly reduced in slow nicotine metabolizers (P = 0.04). Slow metabolizers exhibited greater reductions in cravings after scanning than normal metabolizers; however, craving was unrelated to nAChR availability.The rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies the differences in treatment response between slow and normal metabolizers of nicotine.

SUBMITTER: Dubroff JG

PROVIDER: S-EPMC4646418 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism.

Dubroff Jacob G JG Doot Robert K RK Falcone Mary M Schnoll Robert A RA Ray Riju R Tyndale Rachel F RF Brody Arthur L AL Hou Catherine C Schmitz Alexander A Lerman Caryn C

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20150813 11

<h4>Unlabelled</h4>The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR (α4β2* subtype) availability using PET imaging of the radi ...[more]

PMID: 26272810

Similar Datasets

Project description:IntroductionSmokers who use opioids smoke more cigarettes per day (CPD) than non-opioid users, which could be due to the effects of opioids on nicotine metabolism. Moreover, nicotine metabolism increases during pregnancy, potentially making quitting more difficult for pregnant smokers. We examined nicotine metabolism and its association with opioid use (OU) and CPD in pregnant smokers.MethodsWe recruited pregnant women who smoked at least 5 CPD for a clinical trial of smoking cessation. Plasma nicotine metabolite ratio (NMR; trans-3'-hydroxycotinine (3HC)/cotinine)-a biomarker of nicotine metabolism-OU (involving methadone, buprenorphine, fentanyl, oxycodone, or tramadol), and CPD were assessed at baseline. We used linear regression to examine the associations between log-transformed NMR, OU, and CPD, adjusting for race/ethnicity and menthol smoking.ResultsAmong 129 pregnant smokers, 25 (19%) were opioid users; most were maintained on methadone (n = 14). Compared to non-OU smokers, OU smokers had higher median CPD (10.0 vs. 7.0, p = .0007), serum 3HC (81.0 vs. 42.0 ng/mL, p = .0001), and NMR (0.63 vs. 0.43, p < .0001). In addition, methadone-maintained smokers had a higher median NMR than non-OU smokers (0.66 vs. 0.43, p = .0004). Adjusting for covariates, log-transformed NMR was greater in OU smokers (p = .012), specifically methadone-maintained smokers (p = .024), than non-OU smokers.ConclusionsOur preliminary results show that OU is associated with a higher NMR in pregnant smokers. A larger study sample is needed to replicate this finding, examine potential mechanisms, and determine its clinical significance.ImplicationsAmong pregnant smokers, we observed that nicotine metabolism was significantly faster among opioid users-the majority of whom were on methadone maintenance-compared to nonusers, which could have implications for smoking cessation. Further studies are needed to replicate this finding, evaluate potential mechanisms, and determine its clinical significance.

Dataset Information

Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism.

Publications

Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets