HIV[1]

In a similar manner, dimercaprol (10-100 μM; 4 hours) can significantly protect PC-12 cells from formaldehyde-mediated cell death [2].

Dimercaprol (2,3-Dimercapto-1-propanol; 12.5-75 mg/kg; subcutaneous injection; once) increases the agent and decreases mercury levels in the liver and water [3].

Cell Viability Assay[2]
Cell Types: PC-12 cells
Tested Concentrations: 10, 25, 50 and 100 μM
Incubation Duration: 4 hrs (hours)
Experimental Results: Significant protection of PC-12 cells from acrolein-mediated cell damage in a dose-dependent manner die.

Animal/Disease Models: Wistar rats (13 days old)) injected with HgCl2[3]
Doses: 12.5 mg/kg, 25 mg/kg, 50 mg/kg or 75 mg/kg
Route of Administration: subcutaneous injection; primary
Experimental Results:diminished liver function and mercury levels in the kidneys.

Absorption, Distribution and Excretion
Following intramuscular injection. In urine. Because dimercaprol is a lipophilic drug, it rapidly penetrates into cells. Its highest concentrations are found in the liver, kidneys, brain, and small intestine. Due to its lipophilic nature, complexes formed with mercury and other metals after dimercaprol treatment may redistribute to sensitive cells in the brain. After topical application, dimercaprol is readily absorbed through the skin. The percutaneous absorption rate in rats and humans is 3 mmol/cm² (124 mg) per hour. After absorption, dimercaprol is distributed to all tissues (primarily intracellular), including the brain, with the highest concentrations found in the liver and kidneys. Peak plasma concentrations are reached within 30–60 minutes after intramuscular injection of a therapeutic dose of dimercaprol. Dimercaprol is slowly absorbed through the skin after topical application. Orally administered dimercaprol is not absorbed. After intramuscular injection, it is rapidly absorbed, with effects lasting at least 12 hours. Approximately 80% of the dose is absorbed within 1 hour, and 90% within 6 hours. Peak plasma concentrations are reached within 1 hour. Hepatic metabolism (via glucuronidation) and excretion are largely completed within 4 hours. Dimercaprol is the only commonly used chelating agent that readily crosses cell membranes. Therefore, drug concentrations in certain organs (liver, kidneys, small intestine) can be up to five times higher than in the blood. Metabolism/Metabolites…Metabolic degradation and excretion are largely completed within 4 hours. Dimercaprol is not excreted as a dimercaprol-metal complex but is rapidly metabolized in the liver and excreted in the urine as an inactive product. Biological Half-Life: This drug has a short half-life.

Toxicity Summary
Identification: Dimercaprol is a therapeutic compound originally developed as an antidote for vesicant arsenic gases such as Lewisite. It is a clear to pale yellow liquid with a pungent thiol odor. It is slightly soluble in water and vegetable oils. Peanut oil is commonly used in pharmaceutical preparations. It is miscible with alcohols, benzyl benzoate, ether, methanol, and other solvents. Dimercaprol can be used to treat arsenic (organic and inorganic), gold, and inorganic mercury poisoning. Human Exposure: Major risks include hypertension, tachycardia, cardiovascular failure, convulsions, excitement, hyperglycemia, and hypoglycemia. Extra caution should be exercised when using this antidote if oliguria, hypertension, and liver impairment occur. Target organs are the kidneys, cardiovascular system, and central nervous system. Clinical manifestations include nausea, vomiting, headache, burning sensation in the lips, throat, mouth, and eyes; tearing and salivation; sweating, runny nose, and burning sensation in the penis; tightness or pain in the throat or chest, muscle pain and cramps, and numbness and tingling in the hands; abdominal pain, anxiety, tension and weakness, urticaria, and high fever. It can cause pain and sterile abscesses. Skin and mucous membrane irritation may be observed after local contact. This drug should be administered as soon as possible via deep intramuscular injection; never administer intravenously or subcutaneously. Dimercaprol is well tolerated in children. This drug should not be used for iron, cadmium, tellurium, selenium, vanadium, or uranium poisoning. It is contraindicated in elemental mercury vapor poisoning as it will further increase the mercury content in the brain. This drug is contraindicated in patients with renal insufficiency, hepatic insufficiency, or hypertension. This drug can be absorbed through the skin. Peak plasma concentrations are reached 30-60 minutes after intramuscular injection. Dimercaprol is a lipophilic drug and can rapidly penetrate into cells. The highest drug concentrations are found in the liver, kidneys, brain, and small intestine. Glucuronide conjugates are excreted by the kidneys. Iron therapy should not be administered until at least 24 hours after taking dimercaprol, and the two should not be taken concurrently. Patients may have a thiol-like odor in their breath. Hemolytic anemia has been reported in patients with G6PD deficiency after taking dimercaprol. Dimercaprol may cause a transient decrease in polymorphonuclear leukocytes in children. Animal studies: Animal studies have shown that dimercaprol has a short biological half-life, and its metabolic degradation and renal excretion can be completed within 6–24 hours. In animals, lethal doses of dithiol cause convulsions and severe abdominal muscle spasms, followed by death. Sublethal doses of dimercaprol result in lethargy, lacrimation, conjunctival edema, blepharospasm, salivation, and vomiting. With increasing doses, animals may develop ataxia, hypoalgesia, muscle tremors, nystagmus, tonic and clonic seizures, ultimately leading to death in a coma. In cats, intravenous injection causes cardiovascular depression, manifested as a decrease in systemic and pulmonary artery pressure. Repeated topical application in animals may lead to sensitizing dermatitis. Chronic effects include hepatic steatosis and impaired liver function. In animals, prolonged parenteral administration can increase white blood cell count by 30%. This drug can cause skeletal deformities, growth retardation, and increased embryonic mortality.

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Hepatotoxicity
In clinical trials in children with Wilson's disease, serum transaminase levels typically improved or remained stable during dimercaprol treatment. There are currently no clinical reports of acute liver injury with jaundice caused by dimercaprol. Patients with Wilson's disease typically have mild to moderate elevations in serum transaminases and may present with signs and symptoms of cirrhosis. Improvement of liver damage in Wilson's disease usually requires months to years of treatment. The lack of significant hepatotoxicity of dimercaprol may be due to its low frequency of use, typically short duration of treatment, and other prominent side effects, limiting its long-term use.
Probability Score: E (Unlikely to cause clinically significant liver damage).
Drug Class: Chelating Agent, Wilson's Disease Treatment Drugs
Synthetic Subclass, Wilson's Disease: Penicillamine, Triethylenetetramine, Zinc

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Interactions
...Acute poisoning after intramuscular injection of tellurium oxide in guinea pigs, with severe kidney and liver damage and higher mortality rates when receiving balancing therapy...
Dimercaprol can form toxic complexes with iron, cadmium, selenium, or uranium. Iron therapy should not be administered concurrently with dimercaprol; it is recommended to administer iron therapy at least 24 hours after the last dimercaprol injection. Dimercaprol is a compound used to treat mercury poisoning, but its efficacy is low. It is speculated that the mechanism of action of dimercaprol is through reactivation of targeted thiol-containing proteins. In this study, we investigated the inhibitory effect of mercuric chloride treatment (subcutaneous injection of 2.3 or 4.6 mg/kg HgCl2 for 3 consecutive days) on the activity of δ-aminolevulinic acid dehydratase (ALA-D) in the brain, kidney, and liver of mice, and whether dimercaprol (0.25 mmol/kg, 24 hours after the last mercury injection) could reverse the effects of mercury. The results showed that the injected doses of mercuric chloride did not inhibit the activity of δ-aminolevulinic acid dehydratase in the brain. Dimercaprol treatment failed to restore normal enzyme activity following the 25% inhibition of liver enzyme activity induced by 4.6 mg/kg mercuric chloride (HgCl2). In the kidneys, dimercaprol enhanced the inhibitory effect of 4.6 mg/kg mercuric chloride (from 35% after mercuric chloride alone to 65% after mercuric chloride combined with dimercaprol treatment). Exposure to 2.3 or 4.6 mg/kg mercuric chloride increased the mercury content in the kidneys, and this content was higher than in any other organ. Mercury only accumulated in the liver after exposure to 4.6 mg/kg mercuric chloride, and dimercaprol further increased mercury deposition. Dimercaprol treatment also increased mercury levels in the brain tissue of animals exposed to 4.6 mg/kg mercuric chloride. In vitro experiments showed that enzymes from all sources exhibited similar sensitivity to the combined effects of mercuric chloride and dimercaprol. Without pre-incubation, 0–500 μM dimercaprol enhanced the inhibitory effect of mercuric chloride on δ-aminolevulinic acid dehydratase activity. With pre-incubation, 100 μM and 250 μM dimercaprol enhanced the sensitivity of δ-aminolevulinic acid dehydratase to mercury, while 500 μM dimercaprol partially protected the enzyme from mercury inhibition. When pre-incubated with the enzyme, 500 μM dimercaprol inhibited δ-aminolevulinic acid dehydratase activity in the kidneys and liver. These data suggest that the dimercaprol-mercury complex may be more toxic to δ-aminolevulinic acid dehydratase activity than Hg²⁺. Furthermore, existing data indicate that dimercaprol does not exert its effects by reactivating mercury-inhibited thiol-containing δ-aminolevulinic acid dehydratases, and that it may itself have an inhibitory effect, depending on tissue type. Dimercaprol reduces insulin effectiveness by reducing disulfide bonds. Non-human toxicity values: Mouse intraperitoneal LD50: approx. 125 mg/kg; Rat intraperitoneal LD50: approx. 140 mg/kg; Rat intramuscular LD50: approx. 105 mg/kg

[1]. 2,3 Dimercapto-1-propanol inhibits HIV-1 tat activity, viral production, and infectivity in vitro. AIDS Res Hum Retroviruses. 1990 Jul;6(7):919-27.

[2]. Dimercaprol is an acrolein scavenger that mitigates acrolein-mediated PC-12 cells toxicity and reduces acrolein in rat following spinal cord injury. J Neurochem. 2017 Jun;141(5):708-720.

[3]. 2,3-Dimercapto-1-propanol does not alter the porphobilinogen synthase inhibition but decreases the mercury content in liver and kidney of suckling rats exposed to HgCl2. Basic Clin Pharmacol Toxicol. 2005 Apr;96(4):302-8.

Therapeutic Uses
Antidote; Chelating Agent
Dimercaprol is the first-line antidote for acute poisoning caused by ingestion of arsenic (excluding arsine), mercury, or gold, which may be due to ingestion of salts of these metals or overdose of medications containing these metals. Appropriate supportive care should be provided when administering dimercaprol, and it is most effective when taken early in the course of poisoning. In treating acute mercury salt poisoning, dimercaprol is most effective when taken within 1-2 hours of ingestion, as extensive kidney damage caused by mercury is irreversible. Dimercaprol is ineffective against poisoning by monoalkyl mercury compounds and has little effect on chronic mercury poisoning. Although dimercaprol is generally ineffective in treating allergic reactions to mercury compounds, it is effective for acromegaly (pink disease) caused by mercury poisoning in infants and young children. Dimercaprol is generally effective in treating chronic poisoning by inorganic or organic arsenic compounds, but its effectiveness is minimal if aplastic anemia, hemorrhagic encephalitis, or jaundice has occurred. In one patient with arsenic poisoning complicated by protein-losing enteropathy, hypoalbuminemia and edema improved after treatment with dimercaprol. This drug is ineffective against arsine (AsH3) poisoning. Dermatitis and thrombocytopenia caused by gold poisoning may improve after treatment with dimercaprol. /Uses included on the US product label/
Skin or ocular manifestations of arsenic poisoning can be effectively treated with topical dimercaprol ointment or oil solution, respectively. /Uses not included on the US product label/
Although dimercaprol can chelate lead, for most cases of moderate lead poisoning, other drugs (e.g., calcium edetate sodium (EDTA calcium), dimethyl succinate) are usually the first choice. However, dimercaprol can be used as an adjunct to calcium edetate sodium, and both drugs are preferably used concurrently, at least initially, in the treatment of severe lead poisoning (blood lead concentration exceeding 70 μg/dL) and/or acute lead encephalopathy (most common in children). Compared to sodium edetate alone, the combination of dimercaprol and sodium edetate can increase lead excretion, reduce mortality, and may decrease the incidence of brain injury; however, this combination therapy does not completely eliminate the risk of permanent, severe brain damage. Because lead encephalopathy is extremely rare in adults, experience with the combination of dimercaprol and sodium edetate in adult patients is limited; however, this combination has provided rapid symptom relief in a small number of adult patients with lead encephalopathy. Although the combination of dimercaprol and sodium edetate is also recommended for symptomatic patients with blood lead levels below 70 μg/dL, the American Academy of Pediatrics currently states that, given the toxicity of dimercaprol and the availability of existing alternatives, it should only be used in the most severe cases of lead poisoning (i.e., blood lead levels exceeding 70 μg/dL or the presence of encephalopathy symptoms). For asymptomatic patients with blood lead concentrations of 45-70 μg/dL, calcium edetate sodium is usually used alone (i.e., not in combination with dimercaprol). Dimercaprol is not indicated for acute poisoning caused by alkyl lead compounds (e.g., tetraethyl lead). /See US product label for usage details/
For more complete data on the therapeutic uses of dimercaprol (9 types in total), please visit the HSDB record page.

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Drug Warnings
Dimercaprol has potential nephrotoxicity. Because the chelates dissociate in acidic media, urine should be kept alkaline during dimercaprol treatment to protect the kidneys. Dimercaprol should be used with caution and/or at a reduced dose in patients with oliguria. If acute renal failure occurs during treatment, the drug should be discontinued or used with extreme caution, as serum dimercaprol concentrations may reach toxic levels.
Adverse reactions to dimercaprol are usually mild and transient; approximately half of patients receiving 5 mg/kg intramuscularly will experience adverse reactions. If the dose of dimercaprol exceeds 5 mg/kg, most patients will experience vomiting, seizures, and coma or drowsiness. These symptoms may appear within 30 minutes of injection and usually subside within 1–6 hours. Prophylactic or therapeutic use of ephedrine or antihistamines can prevent or alleviate many of the minor adverse reactions to dimercaprol. The most common adverse reaction is elevated systolic and diastolic blood pressure, which is dose-related and may be accompanied by tachycardia. This usually occurs 15–30 minutes after injection, and blood pressure typically returns to normal within 2 hours. Pain is common at the injection site, and occasionally a sterile abscess may occur, especially if a deep intramuscular injection was not performed. Other possible adverse reactions include nausea, vomiting, headache, sweating, and a feeling of tightness (or pain) in the throat, chest, or hands, which may be accompanied by anxiety, tension, or restlessness, and weakness. Muscle aches, muscle cramps, numbness in the extremities, and abdominal pain have also been reported. Dimercaprol has a strong odor, causing patients to breathe with an unpleasant, thiol-like smell. This drug may also cause a burning sensation in the lips, mouth, throat, eyes, and penis, as well as toothache. Additionally, blepharospasm, conjunctivitis, tearing, runny nose, and drooling may occur. When applied topically, this drug may cause erythema and edema.
For more complete data on drug warnings for dimercaprol (16 in total), please visit the HSDB record page.

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Pharmacodynamics
Because dimercaprol is oily, it cannot be absorbed orally and must be administered via deep intramuscular injection, a procedure that is extremely painful and sensitizing. Studies have found that dimercaprol can promote the transfer of lead to the brain, thereby enhancing its neurotoxic effects. Although dimercaprol can increase cadmium excretion, it also leads to elevated cadmium levels in the kidneys. Therefore, dimercaprol should be avoided in patients with cadmium poisoning.

C3H8OS2

124.23

124.001

59-52-9

3080

Colorless to light yellow liquid

1.2±0.1 g/cm3

223.4±0.0 °C at 760 mmHg

< 25 °C
77 °C

89.1±18.2 °C

0.0±0.9 mmHg at 25°C

1.552

0.64

3

3

2

6

32

0

C(C(CS)S)O

WQABCVAJNWAXTE-UHFFFAOYSA-N

InChI=1S/C3H8OS2/c4-1-3(6)2-5/h3-6H,1-2H2

2,3-bis(sulfanyl)propan-1-ol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

H2O : 41.67 mg/mL (335.43 mM)

Solubility in Formulation 1: 100 mg/mL (804.96 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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