Table 1.

Clinical Trials of Allosteric Modulators, Biased Agonists, and Bivalent Ligands of GPCRs for Treatment of Disorders of the GI Tract or With Side Effects in the GI Tract

Drug	Mechanism of action	Clinical indication	Potential GI effect	Outcome of trial	ClinicalTrials.gov identifier
Allosteric modulators
MK-7622	M1R PAM	Improved cognition in Alzheimer disease	Diarrhea	Trial stopped for futility; diarrhea was most common side effect	NCT01852110
ADX10059	MGLUR5 NAM	GERD	Decreased reflux	Further testing stopped due to increased hepatic transaminases	NCT00820079
Biased agonists
TRV130	MOR agonist	Pain	Decreased nausea and vomiting; constipation not measured in trials	Analgesia comparable to or better than morphine	NCT02335294, NCT02083315
ADL5859	DOR agonist	Pain	Possible decreased effect on GI motility vs MOR agonist; however, not measured in trial	No analgesia	NCT00993863, NCT00626275, NCT00603265, NCT00979953
ADL5747	DOR agonist	Pain	Possible decreased effect on GI motility vs MOR agonist; however, not measured in trial	Not effective for analgesia	NCT00979953, NCT01058642
Oligomer targets
Eluxadoline	MOR agonist and DOR antagonist	IBS-D abdominal pain	Analgesia for abdominal pain	Approved for clinical use	NCT01553747, NCT01553591
Eluxadoline	MOR agonist and DOR antagonist	IBS-D with bile acid Malabsorption	Improved stool consistency	Recruiting	NCT03441581
Eluxadoline	MOR agonist and DOR antagonist	Diarrhea-associated fecal incontinence	Fewer days with fecal incontinence	Recruitment pending	NCT03489265

GI, gastrointestinal.