Lotfipour_2012_Neuropsychopharmacology_37_1738

Reference

Title : A single administration of low-dose varenicline saturates alpha4beta2* nicotinic acetylcholine receptors in the human brain - Lotfipour_2012_Neuropsychopharmacology_37_1738
Author(s) : Lotfipour S , Mandelkern M , Alvarez-Estrada M , Brody AL
Ref : Neuropsychopharmacology , 37 :1738 , 2012
Abstract :

The primary objective of this project was to determine the alpha4beta2(*) 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 alpha4beta2(*) 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 alpha4beta2(*) 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 alpha4beta2(*) nAChRs in the thalamus and brainstem without reducing withdrawal symptoms.

PubMedSearch : Lotfipour_2012_Neuropsychopharmacology_37_1738
PubMedID: 22395733

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Citations formats

Lotfipour S, Mandelkern M, Alvarez-Estrada M, Brody AL (2012)
A single administration of low-dose varenicline saturates alpha4beta2* nicotinic acetylcholine receptors in the human brain
Neuropsychopharmacology 37 :1738

Lotfipour S, Mandelkern M, Alvarez-Estrada M, Brody AL (2012)
Neuropsychopharmacology 37 :1738