Positive allosteric modulators of neuronal nAChRs and studies investigating them as pharmacotherapies for tobacco use disorder

DrugnAChR subtype activityCharacterized in vitro?In vivo findingsReferences
Desformylf-lustrabromine (dFBr)Full activity at α4β2, partial activity at α7YesReduces nicotine self-administration in rats; blocks behavioral signs of nicotine withdrawal in miceSala et al., 2005; Kim et al., 2007; Liu, 2013; Hamouda et al., 2018
NS9283Selective activity at α4β2YesPotentiates the effect of nicotine in the rat drug discrimination assay; acute and repeated dosing reduces nicotine self-administration in ratsGrupe et al., 2013; Mohler et al., 2014; Maurer et al., 2017
CMPISelective activity at α4β2YesN.A.Albrecht et al., 2008; Hamouda et al., 2016
LY 2087101Full activity at α4β2, α4β4, α7YesDoes not potentiate the effect of nicotine in the mouse drug discrimination assayBroad et al., 2006; Moerke et al., 2016
NS1738Selective type I activity at α7YesBlocks behavioral signs of nicotine withdrawal in miceTimmermann et al., 2007; Jackson et al., 2018
CCMISelective type I activity at α7YesN.A.Ng et al., 2007
AVL-3288Selective type I activity at α7YesN.A.Bortz et al., 2016; Gee et al., 2017
PNU-120596Selective type II activity at α7YesEnhances the hypothermic effects of nicotine; blocks behavioral signs of nicotine withdrawal in mice; does not potentiate the effect of nicotine in the mouse drug discrimination assayHurst et al., 2005; Barron et al., 2009; Moerke et al., 2016; Jackson et al., 2018
TQSSelective type II activity at α7YesN.A.Gronlien et al., 2007; Thomsen and Mikkelsen, 2012
A-867744Selective type II activity at α7YesN.A.Faghih et al., 2009
TBS-345, TBS-346, TBS-516, TBS-546, TBS-556Selective type II activity at α7YesN.A.Chatzidaki et al., 2015
RO5126946Selective type II activity at α7YesN.A.Sahdeo et al., 2014
GAT107Selective ago-PAM at α7YesN.A.Thakur et al., 2013; Papke et al., 2014, 2018
B-973Selective ago-PAM at α7YesN.A.Post-Munson et al., 2017
JNJ-39393406Selective activity at α7YesProduces positive outcomes in preclinical rat and mouse models of schizophrenia-induced cognitive impairment; does not reduce cigarette craving or total smoking and does not increase number of quit days in humansWinterer et al., 2013; Perkins et al., 2018
  • N.A., not applicable.