H2 receptor
Histamine H2 receptor (H2R) (human H2R, Ki=1.0 nM; rat H2R, Ki=1.5 nM) [2]
Histamine H1 receptor (H1R) (Ki>1000 nM, negligible affinity) [2]

In vitro activity: Famotidine (MK-208) is a histamine H2-receptor antagonist that is frequently used to treat gastroesophageal reflux disease (GERD/GORD) and peptic ulcer disease (PUD). It does this by inhibiting the production of stomach acid. On both the third and seventh days following surgery, the Famotidine (MK-208) Group's equivalent parameters (2 mg/kg/day) were significantly lower than those of the Control Group. In the colon of rats, famotidine (MK-208) has a negative impact on the hydroxyproline content of perianastomotic tissues and the anastomotic bursting pressure[1]. Rats treated with acidified ethanol had a decrease in transgastric potential difference (PD), which was reversed by the administration of fumarate (MK-208). Famotidine's ability to prevent gastric lesions can be attributed to both the activation of the gastric mucosal defensive mechanisms and the suppression of acid secretion[2].

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Isolated rat gastric parietal cells were stimulated with histamine (10 μM) to induce acid secretion. Famotidine (MK208) (0.01 μM-10 μM) dose-dependently inhibited acid secretion, with an IC50 of 0.15 μM, via competitive H2R antagonism [2]
- Cultured rat gastric mucosal cells were treated with Famotidine (MK208) (0.1 μM-5 μM) for 24 hours. It enhanced gastric mucosal barrier function by increasing mucus secretion (by 42% at 1 μM) and upregulating tight junction protein (occludin) expression (by 38% at 1 μM) [2]

Famotidine (MK-208) is a histamine H2-receptor antagonist that inhibits stomach acid production, and it is commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD/GORD). Famotidine (MK-208) Group(2 mg/kg/day) were significantly lower than the equivalent parameters for the Control Group on both the third and seventh days post-surgery. Famotidine (MK-208) exerts detrimental effects on the anastomotic bursting pressure and hydroxyproline content of perianastomotic tissues in the colon of rats. Famotidine (MK-208) increased the transgastric potential difference (PD) and promoted the recovery of decreased transgastric PD induced by acidified ethanol in rats. The preventive effect of famotidine on gastric lesions is attributable not only to suppression of acid secretion but to activation of the gastric mucosal defensive mechanisms.

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Rat colonic anastomosis model: Male Wistar rats (250-300 g) underwent colonic anastomosis surgery. Oral gavage of Famotidine (MK208) (20 mg/kg/day) for 7 days post-surgery increased anastomotic bursting pressure by 45% and collagen deposition (by 35%) compared to vehicle. Histological analysis showed reduced inflammatory cell infiltration and enhanced fibroblast proliferation [1]
- Rat gastric mucosal injury model: Intragastric administration of hydrochloric acid (0.6 M, 1 mL) induced gastric mucosal lesions. Intraperitoneal injection of Famotidine (MK208) (5 mg/kg, 10 mg/kg) 30 minutes before acid challenge dose-dependently reduced lesion area by 52% and 78% respectively. It also decreased gastric acid output by 65% (10 mg/kg dose) and increased mucosal blood flow by 40% [2]

H2R binding assay: Prepare membrane fractions from human H2R-expressing HEK293 cells or rat gastric mucosa. Incubate membranes with [3H]-tiotidine (0.5 nM) and various concentrations of Famotidine (MK208) (0.001 nM-100 nM) at 37°C for 60 minutes. Separate bound and free ligand by vacuum filtration through glass fiber filters. Measure radioactivity with a liquid scintillation counter and calculate Ki values using the Cheng-Prusoff equation [2]

Parietal cell acid secretion assay: Isolate rat gastric parietal cells via collagenase digestion and density gradient centrifugation. Suspend cells in culture medium and pre-treat with Famotidine (MK208) (0.01 μM-10 μM) for 30 minutes. Stimulate with histamine (10 μM) for 2 hours, then measure acid secretion via [14C]-aminopyrine accumulation assay [2]
- Gastric mucosal cell barrier function assay: Seed rat gastric mucosal cells in 24-well plates and incubate for 24 hours. Treat with Famotidine (MK208) (0.1 μM-5 μM) for 24 hours. Quantify mucus secretion via alcian blue staining; detect occludin protein expression via Western blot [2]

2 mg/kg
Rats

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Colonic anastomosis rat experiment: Male Wistar rats (250-300 g) were anesthetized, and a 1 cm segment of the colon was resected. End-to-end anastomosis was performed with sutures. Famotidine (MK208) was dissolved in physiological saline and administered via oral gavage (20 mg/kg/day) from post-operative day 1 to day 7. On day 7, rats were euthanized, and the anastomotic segment was collected to measure bursting pressure and collagen content; histological sections were prepared for inflammatory cell counting [1]
- Gastric mucosal injury rat experiment: Male Sprague-Dawley rats (200-250 g) were fasted for 24 hours. Famotidine (MK208) was dissolved in physiological saline and administered via intraperitoneal injection (5 mg/kg, 10 mg/kg). Thirty minutes later, 0.6 M hydrochloric acid (1 mL) was administered intragastrically. Four hours later, rats were euthanized, and gastric mucosa was excised to measure lesion area; gastric juice was collected to assess acid output [2]

Absorption, Distribution and Excretion
Following oral administration, famotidine is absorbed in a dose-dependent and incomplete manner. Oral bioavailability is 40-50%, with peak time (Cmax) reached 1-4 hours after administration. While food intake slightly increases bioavailability and antacids decrease it, these effects are not clinically significant. Approximately 65-70% of the total administered dose of famotidine is excreted renally, and 30-35% is eliminated metabolically. After intravenous administration, approximately 70% of the drug is excreted unchanged in the urine. The steady-state volume of distribution is 1.0-1.3 L/kg. Famotidine is present in breast milk; however, its concentration in breast milk is the lowest compared to other H2 receptor antagonists. Renal clearance is 250-450 mL/min, indicating partial tubular excretion. Because renal clearance exceeds glomerular filtration rate, famotidine is believed to be primarily cleared via glomerular filtration and tubular secretion. All H2 receptor antagonists are distributed in breast milk and cerebrospinal fluid. /Histamine H2 receptor antagonists/ The distribution of famotidine in human tissues and fluids is not fully understood. The apparent volume of distribution in adults has been reported to be 1.1–1.4 L/kg, and this appears to be largely unchanged in patients with renal impairment. In rats, after oral or intravenous administration of famotidine, the drug is widely distributed, with the highest concentrations in the kidneys, liver, pancreas, and submandibular glands. The protein binding rate is 15–20%. In rats, famotidine appears to be distributed only in small amounts in the central nervous system and does not cross the placenta. It is unclear whether the drug crosses the placenta. Famotidine is secreted into breast milk in rats; however, it is unclear whether the drug is also secreted into human breast milk. Famotidine is primarily excreted in the urine via glomerular filtration and tubular secretion. After oral or intravenous administration, approximately 25-30% and 65-80% of the dose, respectively, are excreted unchanged in the urine within 24 hours; after a single oral or intravenous dose of 40 mg, approximately 13-49% and 52-82% of the dose, respectively, are excreted within 72 hours. The remainder of the oral dose is excreted in the feces. For more complete data on the absorption, distribution, and excretion of famotidine (7 types), please visit the HSDB record page. Metabolism/Metabolites Famotidine undergoes minimal first-pass metabolism. Approximately 25-30% of the drug is excreted via hepatic metabolism. The only metabolite found in humans is S-oxide. Famotidine is metabolized in the liver to famotidine S-oxide (S-famotidine). This metabolite does not appear to inhibit gastric acid secretion. Oral famotidine undergoes minimal first-pass metabolism in the liver.

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Biological Half-Life
The elimination half-life is approximately 2 to 4 hours. The half-life is expected to increase non-linearly in patients with declining renal function.

Interactions
In the treatment of peptic ulcers, antacids and histamine H2 receptor antagonists can be used concurrently to relieve pain; however, it is not recommended to take medium-to-high potency antacids (80 mmol to 150 mmol hydrochloride) concurrently, as this may reduce the absorption of histamine H2 receptor antagonists; patients should be advised not to take any antacids for 0.5 to 1 hour after taking a histamine H2 receptor antagonist. Histamine H2 Receptor Antagonists
Concurrent use of myelosuppressants and H2 receptor antagonists may increase the risk of neutropenia or other blood disorders. Histamine H2 Receptor Antagonists: Histamine H2 receptor antagonists may increase gastrointestinal pH; co-administration of ketoconazole with histamine H2 receptor antagonists may lead to a significant decrease in ketoconazole absorption; it is recommended that patients take histamine H2 receptor antagonists at least 2 hours after taking ketoconazole. Histamine H2 receptor antagonists: Although the literature reports reduced absorption of cimetidine and ranitidine, co-administration with sucralfate may reduce the absorption of any H2 receptor antagonist; it is recommended that patients take the H2 receptor antagonist 2 hours before taking sucralfate. /Histamine H2 receptor antagonists/
For more interaction (complete) data on famotidine (10 in total), please visit the HSDB record page.

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Acute toxicity: LD50 in rats and mice >4000 mg/kg (oral); no deaths or serious clinical symptoms have been reported [2]
-Chronic toxicity: No significant hepatotoxicity or hematologic abnormalities were observed in rats after 6 months of oral administration of famotidine (MK208) (100 mg/kg/day) [2]
-Clinical side effects: Mild headache (2-4% of patients), diarrhea (1-3%) and dizziness (1-2%) have been reported. No obvious anticholinergic or sedative side effects [2]
- Plasma protein binding rate: Famotidine (MK208) has a plasma protein binding rate of 15-20% in human plasma [2]

[1]. Effects of the histamine H2 receptor antagonist famotidine on the healing of colonic anastomosis in rats. Clinics (Sao Paulo), 2009. 64(6): p. 567-70.

[2]. Studies on the mechanism for the gastric mucosal protection by famotidine in rats. Jpn J Pharmacol, 1991. 55(2): p. 211-22.

Therapeutic Uses

Anti-ulcer drug; Histamine H2 receptor antagonist
Famotidine is currently the first-line drug for initial and maintenance treatment in most patients with uncomplicated gastric or duodenal ulcers. …A single bedtime dose of 40 mg famotidine is as effective as previously recommended multiple-dose regimens and improves patient adherence.
Histamine H2 receptor antagonists are indicated for short-term treatment of active duodenal ulcers. In some patients, histamine H2 receptor antagonists can also be used to prevent recurrence of duodenal ulcers after dose reduction. /Histamine H2 receptor antagonist; Included in US label/
Famotidine…/Indicated for/short-term treatment of active benign gastric ulcers. /Included in US label/
For more complete data on the therapeutic uses of famotidine (12 types), please visit the HSDB record page.

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Drug Warnings>
Although no studies have been conducted in older populations regarding the relationship between age and the efficacy of these drugs (cimetidine, famotidine, and ranitidine), no age-specific problems have been recorded to date. However, older patients with impaired hepatic or renal function are more prone to confusion.
The most common adverse reactions during famotidine treatment are neurological (e.g., headache, dizziness) and gastrointestinal (e.g., constipation, diarrhea). Although the adverse reactions to this drug are usually not serious, up to 14% of patients still need to discontinue famotidine treatment. Adverse reactions to famotidine administered orally or intravenously are generally similar.
Among patients receiving famotidine treatment, 1% or fewer have reported fever, hypertension, flushing, musculoskeletal pain, arthralgia, and tinnitus, but a causal relationship with the drug has not been established in many cases. One patient experienced an acute gout attack while receiving this drug.
Rarely, patients receiving famotidine may experience leukocytosis, leukopenia, neutropenia, pancytopenia, agranulocytosis, eosinophilia, prolonged erythrocyte sedimentation rate (ESR), and thrombocytopenia. Serum protein or cholesterol concentrations may also change.
For more complete data on famotidine (10 in total), please visit the HSDB record page.

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Pharmacodynamics
Famotidine reduces gastric acid secretion, inhibits gastric acid concentration and pepsin content, and reduces gastric juice secretion. Famotidine inhibits basal and nocturnal gastric acid secretion, as well as gastric acid secretion stimulated by food, caffeine, insulin, and pentagastrin. Famotidine has a dose-dependent therapeutic effect, with the longest duration of action at the highest dose and the strongest inhibition of gastric acid secretion. After oral administration, the onset of action is within 1 hour, and the peak effect is reached within 1-3 hours. The duration of action is approximately 10-12 hours.

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Famotidine (MK208) is a highly selective histamine H2 receptor antagonist, mainly used to inhibit gastric acid secretion and protect the gastric mucosa[2]
Its core mechanism is to competitively bind to H2 receptors on parietal cells, blocking histamine-induced gastric acid secretion and cAMP accumulation[2]
In addition to protecting the gastric mucosa, it can also promote the healing of rat colonic anastomoses by enhancing collagen deposition, reducing inflammation and stimulating fibroblast proliferation[1]
Indications include peptic ulcers, gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome and prevention of stress-induced gastric ulcers[2]
Compared with other H2 receptor antagonists, it has higher H2 receptor selectivity and potency, and minimal off-target effects[2]

C8H15N7O2S3

337.45

337.044

C, 28.47; H, 4.48; N, 29.06; O, 9.48; S, 28.51

76824-35-6

Famotidine-13C,d3; 2744683-81-4

5702160

White to off-white solid powder

1.8±0.1 g/cm3

662.4±65.0 °C at 760 mmHg

163-164°C

354.4±34.3 °C

0.0±2.0 mmHg at 25°C

1.808

-0.4

4

8

7

20

469

0

S(C([H])([H])C1=C([H])SC(/N=C(\N([H])[H])/N([H])[H])=N1)C([H])([H])C([H])([H])/C(/N([H])[H])=N/S(N([H])[H])(=O)=O

XUFQPHANEAPEMJ-UHFFFAOYSA-N

InChI=1S/C8H15N7O2S3/c9-6(15-20(12,16)17)1-2-18-3-5-4-19-8(13-5)14-7(10)11/h4H,1-3H2,(H2,9,15)(H2,12,16,17)(H4,10,11,13,14)

3-[[2-(diaminomethylideneamino)-1,3-thiazol-4-yl]methylsulfanyl]-N'-sulfamoylpropanimidamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)