TABLE 2

Clinical uses of histaminergic ligands according to their molecular mechanisms of action: current, proposed, and nontraditional

H₁R				H₂R
Molecular Mechanism of Action	Therapeutic Use	Pharmacological Effect	Reference	Molecular Mechanism of Action	Therapeutic Use	Pharmacological Effect	Reference
	Current	Antiallergic	Bakker et al. (2001), Panula et al. (2015)	Gs/AC/cAMP inhibition	Current	Gastric acid secretion regulation	Panula et al. (2015)
Gq/11 activity blockade; NF-κB inhibition	Repositioning	Analgesia; neurodegenerative disorders; sleep disorders; stress induced hypertension	Krystal et al. (2011), de Almeida et al. (2015), Shan et al. (2015), Apolloni et al. (2016), Rocha et al. (2016), Stein et al. (2016)	Gs/AC/cAMP inhibition	Repositioning	Chronic heart failure; diabetes; colorectal cancer	Pantziarka et al. (2014), Leary et al. (2016), Pini et al. (2016)
Biased agonism; GR crosstalk	Nontraditional	Neuroprotection; anti-inflammatory potentiation	Moniri et al. (2004), Zappia et al. (2015)	Biased agonism	Nontraditional	Gastric acid secretion rebound; AML treatment	Reher et al. (2012a,b), Alonso et al. (2014, 2015)