Identification

Name
Mersalyl
Accession Number
DB09338
Type
Small Molecule
Groups
Experimental
Description

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 It is an outdated drug, and its approval has been discontinued by the FDA.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].

Structure
Thumb
Synonyms
  • Mersal
Product Ingredients
IngredientUNIICASInChI Key
Mersalyl sodium5X1IO031V8492-18-2WWKZBHGJCDECFG-UHFFFAOYSA-L
Categories
UNII
7RDI07K19U
CAS number
486-67-9
Weight
Average: 483.87
Monoisotopic: 485.07623
Chemical Formula
C13H17HgNO6
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

Pharmacology

Indication

Elevated blood pressure, edema [6, 14].

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].

TargetActionsOrganism
UAlkaline phosphatase, tissue-nonspecific isozyme
antagonist
Human
UAquaporin-1Not AvailableHuman
UMonocarboxylate transporter 1
antagonist
Human
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].

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].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcemetacinThe therapeutic efficacy of Mersalyl can be decreased when used in combination with Acemetacin.
AcetaminophenAcetaminophen may decrease the excretion rate of Mersalyl which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Mersalyl which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Mersalyl which could result in a higher serum level.
Adefovir DipivoxilAdefovir Dipivoxil may decrease the excretion rate of Mersalyl which could result in a higher serum level.
AlfentanilThe therapeutic efficacy of Mersalyl can be decreased when used in combination with Alfentanil.
AlmotriptanAlmotriptan may decrease the excretion rate of Mersalyl which could result in a higher serum level.
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Mersalyl.
AlphaprodineThe risk or severity of adverse effects can be increased when Alphaprodine is combined with Mersalyl.
AlprazolamAlprazolam may decrease the excretion rate of Mersalyl which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:1850465]
  2. Thalhammer T, Graf J: Hepatobiliary transport of the anionic organomercury compound (mersalyl) is carrier mediated. Biochem Pharmacol. 1989 Oct 1;38(19):3223-31. [PubMed:2818621]
  3. 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. [PubMed:7408902]
  4. Mersalyl [Link]
  5. Mersalyl [Link]
  6. Mersalyl [Link]
  7. Mercurial Diuretics Their Mechanism of Action and Application [Link]
  8. MIMS: Mersalyl [Link]
  9. Uncouplers and inhibitors [Link]
  10. On the inhibitory action of mersalyl on microsomal drug oxidation: A rigid organization of the electron transport chain [Link]
  11. Mersalyl acid [Link]
  12. Pharmacokinetics and Toxicology of Aluminum in the Brain [Link]
  13. MERSALYL- AN ANTIVIRAL DIURETIC [Link]
  14. Salt and Water Balance [Link]
  15. Metabolic adaptation of renal carbohydrate metabolism. V.In vivo response of rat renal-tubule gluconeogenesis to different diuretics [Link]
External Links
KEGG Compound
C11336
PubChem Compound
443130
PubChem Substance
310265214
ChemSpider
11337655
ChEBI
6771
ChEMBL
CHEMBL1201330
Wikipedia
Mersalyl
ATC Codes
C03BC01 — Mersalyl
MSDS
Download (266 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)377.6 - 379.4MSDS
water solubilitypartially miscible in waterMSDS
Predicted Properties
PropertyValueSource
Water Solubility9.9 mg/mLALOGPS
logP-0.07ALOGPS
logP-0.74ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)3.24ChemAxon
pKa (Strongest Basic)-1.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area105.09 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity69.75 m3·mol-1ChemAxon
Polarizability30.58 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

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
Phenoxyacetate / Phenoxy compound / Phenol ether / Alkyl aryl ether / Carboxylic acid salt / Carboximidic acid / Carboximidic acid derivative / Carboxylic acid derivative / Carboxylic acid / Dialkyl ether
show 16 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid (CHEBI:6771)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Pyrophosphatase activity
Specific Function
This isozyme may play a role in skeletal mineralization.
Gene Name
ALPL
Uniprot ID
P05186
Uniprot Name
Alkaline phosphatase, tissue-nonspecific isozyme
Molecular Weight
57304.435 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Water transmembrane transporter activity
Specific 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 o...
Gene Name
AQP1
Uniprot ID
P29972
Uniprot Name
Aquaporin-1
Molecular Weight
28525.68 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Symporter activity
Specific Function
Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucin...
Gene Name
SLC16A1
Uniprot ID
P53985
Uniprot Name
Monocarboxylate transporter 1
Molecular Weight
53943.685 Da
References
  1. Pharmacokinetics and Toxicology of Aluminum in the Brain [Link]

Enzymes

Kind
Protein
Organism
Human
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
  1. 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. [PubMed:7408902]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phosphoenolpyruvate carboxykinase (gtp) activity
Specific Function
Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the...
Gene Name
PCK1
Uniprot ID
P35558
Uniprot Name
Phosphoenolpyruvate carboxykinase, cytosolic [GTP]
Molecular Weight
69193.975 Da
References
  1. Metabolic adaptation of renal carbohydrate metabolism. V.In vivo response of rat renal-tubule gluconeogenesis to different diuretics [Link]

Drug created on November 26, 2015 17:19 / Updated on October 01, 2018 16:37