Mersalyl
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Identification
- Generic Name
- Mersalyl
- DrugBank Accession Number
- DB09338
- Background
Mersalyl is the sodium salt form of mersalyl acid, a mercurial diuretic. It is an outdated drug, and its approval has been discontinued by the FDA. Mersalyl acid is currently replaced by less toxic non-mercury containing diuretics 4,6. The sodium salt of a mercury-containing derivative of salicylamide, was formerly used (often in combination with theophylline) to treat edema, due to its powerful diuretic properties 6. Interestingly, it has been found to have antiviral properties in mice 13.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
- Weight
- Average: 483.87
Monoisotopic: 485.07623 - Chemical Formula
- C13H17HgNO6
- Synonyms
- Acidum mersalylicum
- Mersal
Pharmacology
- Indication
Elevated blood pressure, edema 6,14.
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- Pharmacodynamics
Mersalyl acid is an organomercuric compound. It is used as a diuretic. Mercury is a heavy, silvery d-block metal and one of six elements that are liquid at or near room temperature and pressure. It is a naturally occuring substance, and combines with other elements such as chlorine, sulfur, or oxygen to form inorganic mercury compounds (salts). Mercury also combines with carbon to make organic mercury compounds 11.
- Mechanism of action
Mersalyl is a mercurial diuretic which acts on the renal tubules, increasing the excretion of sodium and chloride, in approximately equal amounts, and of water 8. As a result, blood pressure and edema is markedly decreased.
High-affinity binding of the divalent mercuric ion to thiol or sulfhydryl groups of proteins is believed to be the major mechanism for the activity of mercury. Through alterations in intracellular thiol status, mercury can promote oxidative stress, lipid peroxidation, mitochondrial dysfunction, and changes in heme metabolism. Mercury is known to bind to microsomal and mitochondrial enzymes, resulting in cell injury and death. For example, mercury is known to inhibit aquaporins, halting water flow across the cell membrane. It also inhibits the protein LCK, which causes decreased T-cell signaling and immune system depression. Mercury is also believed to inhibit neuronal excitability by acting on the postsynaptic neuronal membrane. It also affects the nervous system by inhibiting protein kinase C and alkaline phosphatase, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. Organic mercury exhibits developmental effects by binding to tubulin, which prevents microtubule assembly and causes mitotic inhibition. In addition, mercury produces an autoimmune response, likely by modification of major histocompatibility complex (MHC) class II molecules, self-peptides, T-cell receptors, or cell-surface adhesion molecules 11.
Target Actions Organism UAlkaline phosphatase, tissue-nonspecific isozyme antagonistHumans UAquaporin-1 Not Available Humans UMonocarboxylate transporter 1 antagonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Organic mercury is absorbed primarily in the gastrointestinal tract, followed by distribution throughout the body via the bloodstream. Organic mercury forms a complex with free cysteine and the cysteine and sulfhydryl groups on proteins such as hemoglobin (Hgb). These complexes function to mimic methionine and, as a result, are transported throughout the body. This includes travel across the blood-brain barrier and across the placenta 11.
- Route of elimination
Organic mercury is metabolized into inorganic mercury, which is eventually excreted in the urine and feces 11.
- Half-life
Not Available
- Clearance
The hepatobiliary excretion of mersayl was studied in the isolated perfused rat liver and in isolated rat liver plasma membrane vesicles. In the isolated perfused liver, mersalyl was found to be immediately absorbed by the perfusion medium and concentratively excreted into bile. Uptake is characterized by saturation kinetics (S)0.5 = 20 microM, Vmax = 117 nmoles/min/g liver, cooperatively of mersalyl binding sites, stimulation by extracellular sodium and temperature dependence. Uptake of mersalyl into basolateral membrane vesicles also demonstrates characteristics of a carrier-mediated transport, dependence on extravesicular sodium, cooperativity of mersalyl binding sites, temperature dependence and trans-stimulation by intravesicular non-radioactive mersalyl. Uptake was found to be inhibited by alpha-naphthylacetic acid and mercapto group reagents, suggesting involvement of mercapto groups on the carrier and a binding site for carboxylic anions. Data from the isolated perfused liver and from isolated basolateral vesicles suggest that mersalyl uptake into the liver is carrier mediated. Uptake mechanism and driving forces appear analogous to those for the uptake of chemically related compounds such as taurocholic acid. It is, therefore, speculated that mersalyl may be transported by carrier molecules which accept various chemically unrelated compounds 13.
- Adverse Effects
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- Toxicity
Stomatitis, gastric disturbance, vertigo, febrile reactions, skin eruptions, and irritation may occur with overdose. Thrombocytopenia, neutropenia, and agranulocytosis. Intravenous administration may cause severe hypotension and cardiac arrhythmias, which has been followed by sudden death 8.
Mercury mainly affects the nervous system. Exposure to high levels of metallic, inorganic, or organic mercury can permanently damage the brain, kidneys, and developing fetus. Effects on brain functioning may result in irritability, shyness, tremors, changes in vision or hearing, and memory problems. Acrodynia, a type of mercury poisoning in children, is characterized by pain and pink discoloration of the hands and feet. Mercury poisoning can also cause Hunter-Russell syndrome and Minamata disease 11.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Mersalyl which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Mersalyl which could result in a higher serum level. Acemetacin The therapeutic efficacy of Mersalyl can be decreased when used in combination with Acemetacin. Acetaminophen Acetaminophen may decrease the excretion rate of Mersalyl which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Mersalyl which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- Not Available
Products
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- Product Ingredients
Ingredient UNII CAS InChI Key Mersalyl sodium 5X1IO031V8 492-18-2 WWKZBHGJCDECFG-UHFFFAOYSA-L
Categories
- ATC Codes
- C03BC01 — Mersalyl
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenoxyacetic acid derivatives. These are compounds containing an anisole where the methane group is linked to an acetic acid or a derivative.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Phenoxyacetic acid derivatives
- Direct Parent
- Phenoxyacetic acid derivatives
- Alternative Parents
- Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Carboxylic acid salts / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids / Organic transition metal salts / Carboxylic acids / Monocarboxylic acids and derivatives / Dialkyl ethers show 6 more
- Substituents
- Alkyl aryl ether / Aromatic homomonocyclic compound / Carbonyl group / Carboximidic acid / Carboximidic acid derivative / Carboxylic acid / Carboxylic acid derivative / Carboxylic acid salt / Dialkyl ether / Ether show 16 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- monocarboxylic acid (CHEBI:6771)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 7RDI07K19U
- CAS number
- 486-67-9
- InChI Key
- HQRSUIDICNOLPX-UHFFFAOYSA-M
- InChI
- InChI=1S/C13H16NO5.Hg.H2O/c1-9(18-2)7-14-13(17)10-5-3-4-6-11(10)19-8-12(15)16;;/h3-6,9H,1,7-8H2,2H3,(H,14,17)(H,15,16);;1H2/q;+1;/p-1
- IUPAC Name
- 2-(2-{[3-(hydroxymercurio)-2-methoxypropyl]carbamoyl}phenoxy)acetic acid
- SMILES
- COC(CNC(=O)C1=CC=CC=C1OCC(O)=O)C[Hg]O
References
- General References
- Park CS, Doh PS, Lee CJ, Han DS, Carraway RE, Miller TB: Cellular mechanism of stimulation of renin secretion by the mercurial diuretic mersalyl. J Pharmacol Exp Ther. 1991 Apr;257(1):219-24. [Article]
- Thalhammer T, Graf J: Hepatobiliary transport of the anionic organomercury compound (mersalyl) is carrier mediated. Biochem Pharmacol. 1989 Oct 1;38(19):3223-31. [Article]
- Steven FS, Griffin MM: Studies on the molecular mechanism of mersalyl and 4-aminophenylmercuric acetate re-activation of trypsin-thiol complexes. Eur J Biochem. 1980 Aug;109(2):567-73. [Article]
- Mersalyl [Link]
- Mersalyl [Link]
- Mersalyl [Link]
- Mercurial Diuretics Their Mechanism of Action and Application [Link]
- MIMS: Mersalyl [Link]
- Uncouplers and inhibitors [Link]
- On the inhibitory action of mersalyl on microsomal drug oxidation: A rigid organization of the electron transport chain [Link]
- Mersalyl acid [Link]
- Pharmacokinetics and Toxicology of Aluminum in the Brain [Link]
- MERSALYL- AN ANTIVIRAL DIURETIC [Link]
- Salt and Water Balance [Link]
- Metabolic adaptation of renal carbohydrate metabolism. V.In vivo response of rat renal-tubule gluconeogenesis to different diuretics [Link]
- External Links
- MSDS
- Download (266 KB)
Clinical Trials
- Clinical Trials
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source boiling point (°C) 377.6 - 379.4 MSDS water solubility partially miscible in water MSDS - Predicted Properties
Property Value Source Water Solubility 9.9 mg/mL ALOGPS logP -0.07 ALOGPS logP -0.74 Chemaxon logS -1.7 ALOGPS pKa (Strongest Acidic) 3.24 Chemaxon pKa (Strongest Basic) -1.3 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 105.09 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 69.75 m3·mol-1 Chemaxon Polarizability 30.58 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has broad substrate specificity and can hydrolyze a considerable variety of compounds: however, only a few substrates, such as diphosphate (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate (PLP) and N-phosphocreatine are natural substrates (PubMed:12162492, PubMed:2220817). Plays an essential role in skeletal and dental mineralization via its ability to hydrolyze extracellular diphosphate, a potent mineralization inhibitor, to phosphate: it thereby promotes hydroxyapatite crystal formation and increases inorganic phosphate concentration (PubMed:23688511, PubMed:25982064). Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix (By similarity). Also promotes dephosphorylation of osteopontin (SSP1), an inhibitor of hydroxyapatite crystallization in its phosphorylated state; it is however unclear whether ALPL/TNAP mediates SSP1 dephosphorylation via a direct or indirect manner (By similarity). Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable form of vitamin B6, in order to provide a sufficient amount of PLP in the brain, an essential cofactor for enzymes catalyzing the synthesis of diverse neurotransmitters (PubMed:20049532, PubMed:2220817). Additionally, also able to mediate ATP degradation in a stepwise manner to adenosine, thereby regulating the availability of ligands for purinergic receptors (By similarity). Also capable of dephosphorylating microbial products, such as lipopolysaccharides (LPS) as well as other phosphorylated small-molecules, such as poly-inosine:cytosine (poly I:C) (PubMed:28448526). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating hydrolysis of N-phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation (By similarity). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity)
- Specific Function
- ADP phosphatase activity
- Gene Name
- ALPL
- Uniprot ID
- P05186
- Uniprot Name
- Alkaline phosphatase, tissue-nonspecific isozyme
- Molecular Weight
- 57304.435 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Forms a water-specific channel that provides the plasma membranes of red cells and kidney proximal tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient (PubMed:1373524). Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865)
- Specific Function
- ammonium channel activity
- Gene Name
- AQP1
- Uniprot ID
- P29972
- Uniprot Name
- Aquaporin-1
- Molecular Weight
- 28525.68 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Bidirectional proton-coupled monocarboxylate transporter (PubMed:12946269, PubMed:32946811, PubMed:33333023). Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH (PubMed:12946269, PubMed:33333023). The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter (By similarity). Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis (By similarity). Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart (PubMed:32946811). Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 309-Asp is essential for the conformational transition (PubMed:33333023)
- Specific Function
- carboxylic acid transmembrane transporter activity
- Gene Name
- SLC16A1
- Uniprot ID
- P53985
- Uniprot Name
- Monocarboxylate transporter 1
- Molecular Weight
- 53943.685 Da
References
- Pharmacokinetics and Toxicology of Aluminum in the Brain [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes
- Specific Function
- calcium ion binding
- Gene Name
- ITIH1
- Uniprot ID
- P19827
- Uniprot Name
- Inter-alpha-trypsin inhibitor heavy chain H1
- Molecular Weight
- 101388.49 Da
References
- Steven FS, Griffin MM: Studies on the molecular mechanism of mersalyl and 4-aminophenylmercuric acetate re-activation of trypsin-thiol complexes. Eur J Biochem. 1980 Aug;109(2):567-73. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Cytosolic phosphoenolpyruvate carboxykinase that catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate (OAA) and acts as the rate-limiting enzyme in gluconeogenesis (PubMed:24863970, PubMed:26971250, PubMed:28216384, PubMed:30193097). Regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle (PubMed:24863970, PubMed:26971250, PubMed:28216384, PubMed:30193097). At low glucose levels, it catalyzes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle (PubMed:30193097). At high glucose levels, it catalyzes the anaplerotic conversion of phosphoenolpyruvate to oxaloacetate (PubMed:30193097). Acts as a regulator of formation and maintenance of memory CD8(+) T-cells: up-regulated in these cells, where it generates phosphoenolpyruvate, via gluconeogenesis (By similarity). The resultant phosphoenolpyruvate flows to glycogen and pentose phosphate pathway, which is essential for memory CD8(+) T-cells homeostasis (By similarity). In addition to the phosphoenolpyruvate carboxykinase activity, also acts as a protein kinase when phosphorylated at Ser-90: phosphorylation at Ser-90 by AKT1 reduces the binding affinity to oxaloacetate and promotes an atypical serine protein kinase activity using GTP as donor (PubMed:32322062). The protein kinase activity regulates lipogenesis: upon phosphorylation at Ser-90, translocates to the endoplasmic reticulum and catalyzes phosphorylation of INSIG proteins (INSIG1 and INSIG2), thereby disrupting the interaction between INSIG proteins and SCAP and promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes (PubMed:32322062)
- Specific Function
- carboxylic acid binding
- Gene Name
- PCK1
- Uniprot ID
- P35558
- Uniprot Name
- Phosphoenolpyruvate carboxykinase, cytosolic [GTP]
- Molecular Weight
- 69193.975 Da
References
- Metabolic adaptation of renal carbohydrate metabolism. V.In vivo response of rat renal-tubule gluconeogenesis to different diuretics [Link]
Drug created at November 27, 2015 00:19 / Updated at June 02, 2024 21:56