Table 2.

Effects of nAChR ligands on murine models and human patients with IBD

Ligand	Mechanism of Action	Disease-modifying Mechanisms	Effects on IBD	Ref.
Nicotine	Non-selective agonist	Suppression of MAdCAM-1; reduced regenerative spike action-potentials	Decreased signs and symptoms of DSS-induced colitis in mice Reduced colonic DRG neuron hyperexcitability in DSS-induced colitis in mice	[30,104]
Galantamine	Non-selective PAM	Reduced NF-κB, TNF-α levels, MPO, and neutrophil infiltration	Decreased signs and symptoms of TNBS-induced colitis in mice	[109]
PNU-282987	α7-selective agonist	Reduced infiltration of leucocytes Reduced infiltration of macrophages, and reduced levels of IL-6, and IFN-γ	Attenuated colonic inflammation in DSS-treated mice Decreased signs and symptoms of DSS-induced colitis in mice	[110,115]
PNU-120596	α7-selective PAM	Decreased IL-1β and TNF-α in LPS-treated mice	Decreased symptoms related to anxiety and depression in mice	[116]
GTS-21	partial α7 agonist	Decreased TNF-α in plasma	Probable decreased colonic inflammation in patients with ulcerative colitis	[117]
AR-R17779	α7 agonist	Reduced colonic infiltration of CD4+ and CD8+ lymphocytes; inhibition of macrophage activation	Decreased signs and symptoms of TNBS-induced colitis in mice Decreased signs and symptoms of postoperative ileus in mice	[99,114]
Encenicline	partial α7 agonist	Reduced colonic infiltration of macrophages, neutrophils, and B lymphocytes	Decreased signs and symptoms of TNBS- and DSS induced colitis in mice	[112]
RgIA	α9 antagonist	Reduced levels of colonic TNF-α	Decreased signs and symptoms of DSS-induced colitis in mice	[118]

Dextran sodium sulfate, DSS; a 2,4,6-trinitrobenzene sulfonic acid, TNBS; oxidative enzyme myeloperoxidase, MPO; mucosal vascular addressin cell adhesion molecule-1, MAdCAM-1.