Page last updated: 2024-12-06

muzolimine

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Description

Muzolimine: A pyrazole diuretic with long duration and high capacity of action. It was proposed for kidney failure and hypertension but was withdrawn worldwide because of severe neurological effects. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID41386
CHEMBL ID1697760
CHEBI ID135124
SCHEMBL ID123392
MeSH IDM0014278

Synonyms (48)

Synonym
3-amino-1-(3,4-dichloro-alpha-methylbenzyl)-2-pyrazolin-5-one
5-amino-2-(1-(3,4-dichlorophenyl)-ethyl)-2,4-dihydro-3h-pyrazol-3-one
3-amino-1-(3,4-dichloro-alpha-methylbenzyl)-4,5-dihydro-5-pyrazolon
brn 0660881
muzolimina [inn-spanish]
einecs 259-573-2
bay g 2821
muzolimina [spanish]
3h-pyrazol-3-one, 2,4-dihydro-5-amino-2-(1-(3,4-dichlorophenyl)ethyl)-
edrul
3h-pyrazol-3-one, 5-amino-2-(1-(3,4-dichlorophenyl)ethyl)-2,4-dihydro-
muzoliminum [inn-latin]
muzolimine (usan/inn)
D05093
55294-15-0
bay-g-2821
muzolimine
CHEBI:135124
5-amino-2-[1-(3,4-dichlorophenyl)ethyl]-4h-pyrazol-3-one
CHEMBL1697760
bay-g 2821
muzoliminum
unii-07z36289zx
muzolimina
muzolimine [usan:inn:ban]
07z36289zx ,
SCHEMBL123392
muzolimine [usan]
muzolimine [mi]
muzolimine [who-dd]
3-amino-1-(3,4-dichloro-a-methylbenzyl)-2-pyrazolin-5-one
muzolimine [inn]
muzolimine [mart.]
RLWRMIYXDPXIEX-UHFFFAOYSA-N
3-amino-1-(1-(3,4-dichlorophenyl)ethyl)-1h-pyrazol-5(4h)-one
AKOS028110654
3h-pyrazol-3-one, 5-amino-2-[1-(3,4-dichlorophenyl)ethyl]-2,4-dihydro-
5-amino-2-[1-(3,4-dichlorophenyl)ethyl]-2,4-dihydro-3h-pyrazol-3-one
DTXSID50866476
Q3868794
FT-0759718
DB13801
bay-g 2821; edrul
3-amino-1-[1-(3,4-dichlorophenyl)ethyl]-4,5-dihydro-1h-pyrazol-5-one
EN300-18568082
CS-0026158
HY-106616
5-amino-2-(1-(3,4-dichlorophenyl)ethyl)-2,4-dihydro-3h-pyrazol-3-one

Research Excerpts

Overview

Muzolimine is a loop diuretic with an original chemical structure devoid of the acidic or sulfonamide group known to be necessary for an interaction with Na+K+Cl- cotransport. It has been proposed in the treatment of hypertension.

ExcerptReferenceRelevance
"Muzolimine is a loop diuretic with an original chemical structure devoid of the acidic or sulfonamide group known to be necessary for an interaction with Na+K+Cl- cotransport. "( The effects of muzolimine and urine from muzolimine-treated rats on Na+K+Cl- cotransport in Madin-Darby canine kidney cells.
Barthelmebs, M; Grima, M; Imbs, JL; Michel, B; Stephan, D, 1991
)
2.08
"Muzolimine is a diuretic which has been proposed in the treatment of hypertension. "( [Mechanism of action of the diuretic effect of muzolimine].
Barthelmebs, M; Grima, M; Imbs, JL; Michel, B, 1990
)
1.98
"Muzolimine is a new diuretic which acts on the ascending limb of the loop of Henle and on the distal tubule."( Influence of muzolimine, a new diuretic, on experimental gentamicin nephrotoxicity.
Fillastre, JP; Morin, JP; Olier, B; Toutain, H, 1987
)
1.36
"Muzolimine appears to be an effective and safe antihypertensive agent."( Comparison of the effects of muzolimine and a fixed combination of diuretics in essential hypertension.
Clementy, J; Wicker, P, 1986
)
1.28
"Muzolimine is a loop diuretic with both the dose-dependent increasing effectiveness of loop diuretics and the long-lasting effect of thiazides. "( Effects of a new loop diuretic (muzolimine) in cirrhosis with ascites: comparison with furosemide.
Bernardi, M; De Palma, R; Gasbarrini, G; Motta, R; Patrono, D; Santini, C; Servadei, D; Trevisani, F,
)
1.86
"Muzolimine is a diuretic with chemical features different from all other known diuretics, and its use seem to be particularly interesting in patients with chronic renal failure. "( Muzolimine in chronic renal failure: a study in 16 patients.
Colla, L; Dogliani, M; Squiccimarro, G; Stratta, P; Vercellone, A, 1985
)
3.15

Actions

Muzolimine 20 mg did not increase mean 24 h urinary Na+ output significantly with respect to placebo.

ExcerptReferenceRelevance
"Muzolimine: 1) increase PRA (11.8 +/- 1.06 vs. "( Interactions between muzolimine, PgE2 and the renin-angiotensin-aldosterone system.
Antonello, A; Bardini, R; Borsatti, A; Calò, L; Cantaro, S; Piccoli, A; Vianello, A, 1985
)
2.03
"Muzolimine 20 mg did not increase mean 24 h urinary Na+ output significantly with respect to placebo."( The effects of single doses of muzolimine upon urinary solute and fluid excretion.
Leary, WP; Reyes, AJ; van der Byl, K, 1985
)
1.28

Treatment

Muzolimine pretreatment of rats for 2 months did not influence the elastin content of arterial tissue or [3H]glycine incorporation into aorticElastin under organ culture conditions. After labelling the elASTin with [4,5-3H)lysine, the [3 h]desmosine and [3h]-isodesmosine isolated from the elasts was lower than that of control animals. Treatment with muzolIMine by food (in a concentration of 800 ppm for four days) and additional oral gavage one hour prior to ischemia prevented the sequelae of ischemie to a great extent.

ExcerptReferenceRelevance
"Muzolimine pretreatment of rats for 2 months did not influence the elastin content of arterial tissue or [3H]glycine incorporation into aortic elastin under organ culture conditions, but after labelling the elastin with [4,5-3H]lysine, the [3H]desmosine and [3H]-isodesmosine isolated from the elastin of muzolimine-pretreated rats and incorporated under organ culture conditions was lower than that of control animals."( Influence of muzolimine on arterial wall elastin.
Buddecke, E; Busse, WD; Garthoff, B; Gau, W; Ritter, W; Schmidt, A; Wünsche, C, 1984
)
1.36
"Treatment with muzolimine by food (in a concentration of 800 ppm for four days) and additional oral gavage one hour prior to ischemia prevented the sequelae of ischemia to a great extent."( Beneficial effect of muzolimine in postischemic acute renal failure in rats.
Garthoff, B, 1985
)
0.93

Pharmacokinetics

Muzolimine has a 14-hour biological half-life in plasma. The pharmacokinetic parameters of muzlimine are as follows.

ExcerptReferenceRelevance
" The excreted urinary volume was measured, and blood was taken at relevant times in order to follow the pharmacokinetic profile."( Pharmacodynamic and pharmacokinetic correlation of muzolimine with and without aluminium hydroxide.
Baykal, N; Hanisch, M; Hey, B; Lücker, PW; Ritter, W; Venitz, J, 1985
)
0.52
" The peak concentration was significantly higher on day 28."( Pharmacokinetics and pharmacodynamics of muzolimine in chronic heart failure.
Bjørnstad, H; Mølstad, P; Storstein, L, 1985
)
0.54
" Pharmacokinetic data observed in advanced renal failure (creatinine clearance between 10 and 30 ml/min) are similar to those observed in healthy subjects or patients with normal renal function."( Diuretic effect and pharmacokinetic data observed at different stages of chronic renal failure with 240 mg of muzolimine.
Baumelou, A; Brouard, R; Chickh-Touami, C; Martre, H; Merdjan, H; Patte, R; Ritter, W; Singlas, E, 1985
)
0.48
" Mean biological half-life of muzolimine in plasma was 14."( Pharmacokinetics and saluretic effect of muzolimine in severe cardiac failure.
Brørs, O; Fauchald, P; Jacobsen, S; Lind, E, 1980
)
0.82

Bioavailability

ExcerptReferenceRelevance
"The influence of food on the bioavailability of muzolimine was investigated in a non-controlled cross-over study."( Food and muzolimine interaction.
Hanisch, M; Lietz, U; Ritter, W; Wingender, W, 1985
)
0.94

Dosage Studied

Muzolimine has more rapid absorption, higher peak concentrations, and increased area under the other plasma concentration curves.

ExcerptRelevanceReference
"We report on 7 patients (2 women, 5 men) with chronic renal failure, who developed under a high dosage of the new diuretic muzolimine (range 240 to 1440 mg per day) fatal neuromyeloencephalopathy."( Muzolimine-induced severe neuromyeloencephalopathy: report of seven cases.
Berlit, P; Gretz, N; Maibach, EA; Pohlmann-Eden, B, 1991
)
1.93
" Each rat was given gentamicin intraperitoneally in a dosage that induces morphological and functional modifications in the kidneys (20 mg/kg/day for 7 days)."( [Can gentamicin nephrotoxicity in rats be modified by chronic administration of muzolimine?].
Fillastre, JP; Morin, JP; Olier, B; Toutain, H, 1986
)
0.5
" M at a lower dosage than F has demonstrated an effective diuretic response irrespective the degree of renal impairment."( Step-dose of muzolimine at different stages of chronic renal failure: comparison with furosemide.
Bazzato, G; Coli, U; Fracasso, A; Landini, S; Morachiello, P; Righetto, F; Scanferla, F, 1985
)
0.64
" Urine collected at 3, 6, 9, 12 and 24 h after dosing was analysed for solutes."( The effects of single doses of muzolimine upon urinary solute and fluid excretion.
Leary, WP; Reyes, AJ; van der Byl, K, 1985
)
0.56
" This is further supported by the fact that at the maximum of the dose-response curves for muzolimine and furosemide in rats, a combination of maximal oral doses still results in significantly higher sodium excretion."( Beneficial effect of muzolimine in postischemic acute renal failure in rats.
Garthoff, B, 1985
)
0.81
" These preliminary data indicate a change in the pharmacokinetics of muzolimine on chronic dosing with more rapid absorption, higher peak concentrations, and increased area under the other plasma concentration curves."( Pharmacokinetics and pharmacodynamics of muzolimine in chronic heart failure.
Bjørnstad, H; Mølstad, P; Storstein, L, 1985
)
0.77
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
dichlorobenzeneAny member of the class of chlorobenzenes carrying two chloro groups at unspecified positions.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (3)

Assay IDTitleYearJournalArticle
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (86)

TimeframeStudies, This Drug (%)All Drugs %
pre-199075 (87.21)18.7374
1990's10 (11.63)18.2507
2000's0 (0.00)29.6817
2010's1 (1.16)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 18.47

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index18.47 (24.57)
Research Supply Index4.75 (2.92)
Research Growth Index3.93 (4.65)
Search Engine Demand Index18.60 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (18.47)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials25 (27.78%)5.53%
Reviews2 (2.22%)6.00%
Case Studies4 (4.44%)4.05%
Observational0 (0.00%)0.25%
Other59 (65.56%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]