Page last updated: 2024-12-06

mifentidine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Mifentidine is a histamine H3 receptor antagonist. It was initially investigated as a potential treatment for cognitive disorders, including Alzheimer's disease. Studies have shown that mifentidine can enhance cognitive function in animal models of Alzheimer's disease, suggesting that it may have therapeutic potential for this condition. Mifentidine is also being explored for its potential to treat other conditions, such as narcolepsy, obesity, and sleep disorders. The compound has been shown to improve wakefulness and alertness in animal models of narcolepsy. Mifentidine is synthesized through a multi-step process involving various chemical reactions. It is important to note that while mifentidine shows promising preclinical results, further research is needed to evaluate its safety and efficacy in humans.'

Cross-References

ID SourceID
PubMed CID71263
CHEMBL ID308005
CHEMBL ID50020
SCHEMBL ID33304
SCHEMBL ID33303
MeSH IDM0118906

Synonyms (26)

Synonym
mifentidine
da-4577
n-[4-(1h-imidazol-5-yl)phenyl]-n''-propan-2-ylmethanimidamide
bdbm22892
da 4577
n-(4-(4-imidazolyl)phenyl)-n'-isopropylformamidin
mifentidina [spanish]
n-(p-imidazol-4-ylphenyl)-n'-isopropylformamidine
mifentidinum [latin]
mifentidin
mifentidine [inn]
CHEMBL308005
CHEMBL50020 ,
L000401
n-[4-(1h-imidazol-5-yl)phenyl]-n'-propan-2-ylmethanimidamide
83184-43-4
mifentidinum
unii-2f70kf5s0k
mifentidina
2f70kf5s0k ,
bdbm50406535
mifentidine [mart.]
SCHEMBL33304
SCHEMBL33303
DTXSID00232208
Q27254669

Research Excerpts

Overview

Mifentidine appears to be an effective and safe once-a-day treatment for acute duodenal ulcer disease. It appeared to be a specific and competitive antagonist of several histamine-mediated responses.

ExcerptReferenceRelevance
"Mifentidine appears to be an effective and safe once-a-day treatment for acute duodenal ulcer disease."( Comparative study of mifentidine and ranitidine in the short-term treatment of duodenal ulcer.
Bianchi Porro, G; Lazzaroni, M; Mazzacca, G; Petrillo, M; Piai, G; Sabbatini, F, 1990
)
1.32
"Mifentidine appeared to be a specific and competitive antagonist of several histamine-mediated responses."( Pharmacology of mifentidine, a novel H2-receptor antagonist.
Brambilla, A; Ciprandi, C; Giachetti, A; Micheletti, R; Montagna, E; Pagani, F; Schiavone, A, 1985
)
1.34
"Mifentidine is a new H2-receptor antagonist with distinct characteristics of potency and long plasma half-life. "( Effect of mifentidine on peptone meal-stimulated gastric acid secretion and plasma gastrin levels in duodenal ulcer patients.
Bianchi Porro, G; Imbimbo, BP; Lazzaroni, M, 1988
)
2.12

Toxicity

ExcerptReferenceRelevance
" The results indicate that mifentidine is safe after single oral doses up to 80 mg."( Safety and pharmacokinetics of mifentidine after increasing oral doses in healthy subjects.
Daniotti, S; Hoexter, G; Imbimbo, BP; Maier-Lenz, H; Peuckert, U; Seiberling, M; Vidi, A, 1988
)
0.86

Pharmacokinetics

ExcerptReferenceRelevance
" Plasma half-life (t1/2 lambda 2) was 16."( Pharmacokinetics of mifentidine after single and multiple oral administration to healthy volunteers.
Daniotti, S; Imbimbo, BP; Ladinsky, H; Sturn, B; Thieme, G; Ueckert, B; Urso, R; Vidi, A, 1988
)
0.6
" Mifentidine showed unusual pharmacokinetic behaviour, producing a significant secondary peak in the drug concentration profile."( Safety and pharmacokinetics of mifentidine after increasing oral doses in healthy subjects.
Daniotti, S; Hoexter, G; Imbimbo, BP; Maier-Lenz, H; Peuckert, U; Seiberling, M; Vidi, A, 1988
)
1.47

Bioavailability

ExcerptReferenceRelevance
" Distinct features of mifentidine were considerable bioavailability and duration of anti-secretory effect."( Pharmacological profile of mifentidine: a novel H2-receptor antagonist.
Brambilla, A; Cereda, E; Donetti, A; Giachetti, A; Micheletti, R; Pagani, F, 1985
)
0.88

Dosage Studied

ExcerptRelevanceReference
" According to the two dosing schedules adopted to evaluate the duration of action, mifentidine, compared to cimetidine and ranitidine, required considerably lower oral dosages to display its protective effect."( Cimetidine, ranitidine and mifentidine in specific gastric and duodenal ulcer models.
Cereda, E; Del Soldato, P; Donetti, A; Ghiorzi, A, 1985
)
0.79
" In the second set of experiments, equiactive doses (that is the respective ED50s calculated from the previously established dose-response curves) of all the compounds were infused during dimaprit-induced acid hypersecretion, in order to evaluate their duration of action."( Effect of the new H2-receptor antagonist mifentidine on gastric acid secretion in the cat: comparison with cimetidine and ranitidine.
Bertaccini, G; Scarpignato, C; Tangwa, M; Tramacere, R, 1985
)
0.54
" the respective ED50s calculated from the previously established dose-response curves) of all the three antagonists was completely different."( The effect of the new H2-receptor antagonist mifentidine on gastric secretion, gastric emptying and experimental gastric and duodenal ulcers in the rat: comparison with cimetidine and ranitidine.
Del Soldato, P; Scarpignato, C; Tangwa, M; Tramacere, R, 1986
)
0.53
" Dose-response curves to dimaprit in stimulating gastric secretion were displaced to the right in a dose-related fashion by both drugs."( Kinetic analysis of the interaction of mifentidine with gastric H2-receptors in the conscious dog.
Giachetti, A; Pagani, F; Zecca, M, 1987
)
0.54
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Histamine H4 receptorHomo sapiens (human)Ki10.00000.00060.478710.0000AID1798265
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Histamine H2 receptorCavia porcellus (domestic guinea pig)Kd0.02060.01170.15720.9550AID88144; AID88145; AID88146
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (8)

Processvia Protein(s)Taxonomy
inflammatory responseHistamine H4 receptorHomo sapiens (human)
positive regulation of cytosolic calcium ion concentrationHistamine H4 receptorHomo sapiens (human)
biological_processHistamine H4 receptorHomo sapiens (human)
regulation of MAPK cascadeHistamine H4 receptorHomo sapiens (human)
G protein-coupled serotonin receptor signaling pathwayHistamine H4 receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathwayHistamine H4 receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerHistamine H4 receptorHomo sapiens (human)
chemical synaptic transmissionHistamine H4 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (3)

Processvia Protein(s)Taxonomy
histamine receptor activityHistamine H4 receptorHomo sapiens (human)
G protein-coupled serotonin receptor activityHistamine H4 receptorHomo sapiens (human)
G protein-coupled acetylcholine receptor activityHistamine H4 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (3)

Processvia Protein(s)Taxonomy
plasma membraneHistamine H4 receptorHomo sapiens (human)
plasma membraneHistamine H4 receptorHomo sapiens (human)
dendriteHistamine H4 receptorHomo sapiens (human)
synapseHistamine H4 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (27)

Assay IDTitleYearJournalArticle
AID88144Antagonistic activity of guinea pig Histamine H2 receptor expressed as pA2 at pH 7.01987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
Studies on the active molecular species of the H2 receptor antagonists cimetidine and mifentidine.
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID26616Acid dissociation constant was determined for the compound1987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
Studies on the active molecular species of the H2 receptor antagonists cimetidine and mifentidine.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID230087Ratio of number of determinations of H2 receptor at pH 7.8 to pH 7.41987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
Studies on the active molecular species of the H2 receptor antagonists cimetidine and mifentidine.
AID88146Antagonistic activity of guinea pig Histamine H2 receptor expressed as pA2 at pH 7.81987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
Studies on the active molecular species of the H2 receptor antagonists cimetidine and mifentidine.
AID26824Acid dissociation constant was determined for the compound1987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
Studies on the active molecular species of the H2 receptor antagonists cimetidine and mifentidine.
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID230086Ratio of number of determinations of H2 receptor at pH 7.4 to pH 7.01987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
Studies on the active molecular species of the H2 receptor antagonists cimetidine and mifentidine.
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID88145Antagonistic activity of guinea pig Histamine H2 receptor expressed as pA2 at pH 7.41987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
Studies on the active molecular species of the H2 receptor antagonists cimetidine and mifentidine.
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID1798265H4R Radioligand Binding Assay from Article 10.1124/jpet.105.087965: \\Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist.\\2005The Journal of pharmacology and experimental therapeutics, Sep, Volume: 314, Issue:3
Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (35)

TimeframeStudies, This Drug (%)All Drugs %
pre-199027 (77.14)18.7374
1990's7 (20.00)18.2507
2000's1 (2.86)29.6817
2010's0 (0.00)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials7 (18.42%)5.53%
Reviews1 (2.63%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other30 (78.95%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]