Famotidine

Famotidine (MK-208) is an orally active and highly selective histamine H2 receptor antagonist. It inhibits gastric acid secretion by blocking the Gs signaling pathway, and regulates intracellular cAMP and ERK pathways. Famotidine inhibits TLR3-mediated inflammatory pathways, and reduces the expression of various inflammatory mediators and interferon-related genes. Famotidine scavenges DPPH and nitric oxide free radicals, alleviates oxidative stress damage in gastric tissue, inhibits proMMP-9, improves vascular endothelial permeability, and restores the normal physiological functions of neutrophils and eosinophils. Famotidine crosses intestinal epithelial cells via facilitated diffusion and passive diffusion, blocks paracellular cation transport, and increases intestinal transepithelial electrical resistance. Famotidine reduces serum levels of transaminases and alkaline phosphatase, exerts analgesic effects and gastric protective effects simultaneously. Famotidine can be used in studies related to COVID-19, liver injury and acute gastric ulcer^{[1][2][3][4][5]}. In Vitro:Famotidine (50 μM; 12 h) inhibits Histamine (HY-B1204)-induced TLR3 mRNA expression in A549 cells without affecting TLR7 expression; it also suppresses the cumulative upregulation of TLR3 expression in A549 cells co-treated with Histamine and poly (I:C) (HY-107202)^[1].
Famotidine (50 μM; 12 h preincubation, 1 h or 12 h poly (I:C) treatment) inhibits Histamine-enhanced TLR3-dependent activation of the TBK1/IRF3 and NF-κB pathways, and reduces the expression of downstream genes in poly (I:C)-treated A549 cells^[1].
Famotidine (50 μM; 12 h preincubation, 24 h SARS-CoV-2 infection) reduces the expression of TLR3 in SARS-CoV-2-infected Caco-2 cells, inhibits the Histamine-enhanced TLR3-dependent signaling pathway, and downregulates the mRNA levels of downstream inflammatory mediators; it also exerts an inhibitory effect on the Histamine-enhanced TLR3-dependent signaling pathway in SARS-CoV-2-infected Caco-2 cells^[1].
Famotidine is a selective inverse agonist and biased arrestin partial agonist for the human histamine H₂ receptor, with a binding affinity of 14 nM, an inverse agonist potency of 33 nM, and an EC₅₀ of 105 nM for arrestin recruitment. It does not exhibit significant interactions with H₁, H₃, or H₄ receptors^[2].
Famotidine induces a concentration-dependent, saturable increase in transepithelial electrical resistance (TEER) across Caco-2 cell monolayers via interaction with paracellular anion sites rather than tight junction tightening, reaching 193% of the control group at 25 mM^[5].
Famotidine undergoes apical-to-basolateral transport across Caco-2 cell monolayers via a combination of saturable facilitated diffusion and non-saturable passive diffusion, with its P_app value decreasing exponentially with concentration; it selectively inhibits the apical-to-basolateral transport of the cationic Ranitidine (HY-B0693) across Caco-2 cell monolayers, indicating that it targets cation-selective conductance via paracellular anion sites^[5]. In Vivo:Famotidine (5-40 mg/kg; i.p.; single dose) exerts dose-dependent antinociceptive activity in the mouse hot plate test^[3].
Famotidine (10-40 mg/kg; i.p.; daily; 3 days) pretreatment for three consecutive days dose-dependently reduces carbon tetrachloride-induced hepatotoxicity in mice, as evidenced by significant decreases in serum ALT and ALP levels^[3].
Famotidine (10-60 mg/kg bw; p.o.; single dose; 30 min before ethanol) dose-dependently protects against ethanol-induced acute gastric ulcer in rats, and suppressing oxidative stress, inflammatory cell infiltration, and proinflammatory cytokine secretion^[4].