TABLE 3.

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

Drug	nAChR subtype activity	Characterized in vitro?	In vivo findings	References
Desformylf-lustrabromine (dFBr)	Full activity at α4β2, partial activity at α7	Yes	Reduces nicotine self-administration in rats; blocks behavioral signs of nicotine withdrawal in mice	Sala et al., 2005; Kim et al., 2007; Liu, 2013; Hamouda et al., 2018
NS9283	Selective activity at α4β2	Yes	Potentiates the effect of nicotine in the rat drug discrimination assay; acute and repeated dosing reduces nicotine self-administration in rats	Grupe et al., 2013; Mohler et al., 2014; Maurer et al., 2017
CMPI	Selective activity at α4β2	Yes	N.A.	Albrecht et al., 2008; Hamouda et al., 2016
LY 2087101	Full activity at α4β2, α4β4, α7	Yes	Does not potentiate the effect of nicotine in the mouse drug discrimination assay	Broad et al., 2006; Moerke et al., 2016
NS1738	Selective type I activity at α7	Yes	Blocks behavioral signs of nicotine withdrawal in mice	Timmermann et al., 2007; Jackson et al., 2018
CCMI	Selective type I activity at α7	Yes	N.A.	Ng et al., 2007
AVL-3288	Selective type I activity at α7	Yes	N.A.	Bortz et al., 2016; Gee et al., 2017
PNU-120596	Selective type II activity at α7	Yes	Enhances 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 assay	Hurst et al., 2005; Barron et al., 2009; Moerke et al., 2016; Jackson et al., 2018
TQS	Selective type II activity at α7	Yes	N.A.	Gronlien et al., 2007; Thomsen and Mikkelsen, 2012
A-867744	Selective type II activity at α7	Yes	N.A.	Faghih et al., 2009
TBS-345, TBS-346, TBS-516, TBS-546, TBS-556	Selective type II activity at α7	Yes	N.A.	Chatzidaki et al., 2015
RO5126946	Selective type II activity at α7	Yes	N.A.	Sahdeo et al., 2014
GAT107	Selective ago-PAM at α7	Yes	N.A.	Thakur et al., 2013; Papke et al., 2014, 2018
B-973	Selective ago-PAM at α7	Yes	N.A.	Post-Munson et al., 2017
JNJ-39393406	Selective activity at α7	Yes	Produces 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 humans	Winterer et al., 2013; Perkins et al., 2018

N.A., not applicable.