![]() | |
![]() Chemical structure (top) and sample of pure compound (bottom) | |
Clinical data | |
---|---|
Routes of administration | Oral |
Drug class | Uncoupling agents |
Legal status | |
Legal status |
|
Pharmacokinetic data | |
Metabolism | Nitro reduction |
Elimination half-life | Unknown |
Identifiers | |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.000.080 |
Chemical and physical data | |
Formula | C6H4N2O5 |
Molar mass | 184.107 g·mol−1 |
3D model (JSmol) | |
| |
|
2,4-Dinitrophenol (2,4-DNP or simply DNP) is an organic compound with the formula HOC6H3(NO2)2. It has been used in explosives manufacturing and as a pesticide and herbicide.
In humans, DNP causes dose-dependent mitochondrial uncoupling, causing the rapid loss of ATP as heat and leading to uncontrolled hyperthermia—up to 44 °C (111 °F)—and death in case of overdose. Researchers noticed its effect on raising the basal metabolic rate in accidental exposure and developed it as one of the first weight loss drugs in the early twentieth century. DNP was banned from human use by the end of the 1930s due to its risk of death and toxic side effects. DNP continues to be used after its ban and experienced a resurgence in popularity after it became available on the Internet.
DNP has the chemical formula HOC6H3(NO2)2. As a solid, it is a yellow, crystalline and has a sweet, musty odor. [1] [2] It sublimates, is volatile with steam, and is soluble in most organic solvents as well as aqueous alkaline solutions. [2] DNP is a member of the dinitrophenols chemical family. [1]
DNP can be produced by hydrolysis of 2,4-dinitrochlorobenzene. [1] [3] Other routes of DNP synthesis include nitration of monochlorobenzene, nitration of benzene with nitrogen dioxide and mercurous nitrate, oxidation of 1,3-dinitrobenzene, [4] and nitration of phenol with nitric acid. [5]
A dust explosion is possible with DNP in powder or granular form in the presence of air. DNP may explosively decompose when submitted to shock, friction or concussion, and may explode upon heating. [6] DNP forms explosive salts with strong bases as well as ammonia, and emits toxic fumes of nitrogen dioxide when heated to decomposition. [7] DNP's explosive strength is 81% that of TNT, based on the Trauzl lead block test. [8]
Historically, DNP has been used as an antiseptic and as a non-selective bioaccumulating pesticide. [9]
DNP was particularly useful as a herbicide alongside other closely related dinitrophenol herbicides like 2,4-dinitro-o-cresol (DNOC), dinoseb and dinoterb. [10] Since 1998 DNP has been withdrawn from agricultural use. [11] Currently, there are no actively registered pesticides containing DNP in the United States or Europe. [12] [13] Dinoseb is used industrially as a polymerisation inhibitor during styrene production. In 2023, the Home Office said it could not determine any legitimate industrial uses for DNP in the United Kingdom. [14]
It is a chemical intermediate in the production of sulfur dyes, [3] wood preservatives [9] and picric acid. [15] A precursor to 2,4,6-trinitrotoluene (TNT), DNP has also been used to make photographic developers and explosives. [16] [17] DNP is classified as an explosive in the United Kingdom [18] and the United States. [19]
DNP raises energy expenditure by 30 to 40 percent and causes a weight loss of 0.7–0.9 kilograms (1.5–2.0 lb) per week. [21] Although DNP is no longer in clinical use as a weight loss drug due to its dangerous side effects, its mechanism of action remains under investigation as a potential approach for treating obesity and non-alcoholic fatty liver disease. [1] [22] [23] Researchers developed a prodrug, HU6, which is metabolized to DNP in the liver to provide more stable blood concentrations. HU6 completed a phase II trial in which it produced significant reductions in liver fat and body weight in overweight people with elevated liver fat, without serious adverse effects. [24]
DNP is used by bodybuilders, fitness enthusiasts, and people with an eating disorder to lose weight. The user profile is similar to that of anabolic steroids; many perceive it to be effective and with manageable risks. [25] Despite health warnings from regulators, DNP is readily available online [25] sometimes under other names such as Dinosan, Dnoc, Solfo Black, Nitrophen, Aldifen, and Chemox. [17] [25] DNP is often sold in tablets containing 100 to 200 mg [1] and may be sold alongside other substances such as anabolic steroids and thyroxine. [17] It may also be found as a contaminant in other bodybuilding supplements not advertised as containing DNP. [25] Online message boards provide information on dosage and regimens for DNP use, and describe the risks of taking the compound and provide advice on how to mitigate hyperthermia. [17] [25] [26] According to a study published in 2023, the most commonly reported doses were between 150 and 300 mg/day. [20] Between 2010 and 2020, reports of overdoses were higher in Australasia, Europe and North America than in Asia, Africa, and South or Central America. [27]
It is also used as a suicide method. [17]
In living cells, DNP acts as a protonophore, an agent that can shuttle protons (hydrogen cations) across biological membranes. It dissipates the proton gradient across the mitochondrial membrane, collapsing the proton motive force that the cell uses to produce most of its ATP chemical energy. Instead of producing ATP, the energy of the proton gradient is lost as heat. [17] The inefficiency is proportional to the dose of DNP that is taken. As the dose increases and energy production is made more inefficient, metabolic rate increases (and more fat is burned) in order to compensate for the inefficiency and to meet energy demands. DNP is probably the best known agent for uncoupling oxidative phosphorylation. The phosphorylation of adenosine diphosphate (ADP) by ATP synthase gets disconnected or uncoupled from oxidation.[ citation needed ]
DNP raises the basal metabolic rate (BMR) and lowers T4 (thyroid hormone) levels by increasing T4 metabolism and reducing thyroid hormone secretion. Because it binds to thyroxine-binding globulin, overall thyroid function may not be affected. DNP cannot substitute for thyroid hormone in myxedema. [28]
Information about pharmacokinetics and pharmacodynamics of DNP in humans is limited. [23] DNP is metabolized via nitro reduction. Its major metabolites are 2-amino-4-nitrophenol and 4-amino-2-nitrophenol. [16] In overdoses, symptom onset can be as soon as 3 hours and the average time to death was 14 hours. [16] [17]
Although many militaries are replacing traditional 2,4,6-trinitrotoluene (TNT)-based explosives for insensitive munitions, DNP is a degradation byproduct of the IMX-101 insensitive munition used by the United States Army. [29]
While the Meisenheimer charge transfer reaction is effective at detecting TNT, it is not effective at detecting many other explosives including DNP. Researchers are studying colorimetric detection and other methods for DNP to find if water or solids such as soils are contaminated with DNP. [30] [31] [32] [33] UiO-66-NH2 can be used to bind to and remove DNP from solution. [34]
DNP has a low therapeutic index, meaning that the dosage at which toxicity occurs is not much larger than that required to produce a desired effect. [17] Individual tolerance to DNP's harmful short- and long-term effects varies greatly. [1] The most common adverse effect reported is a rash, which could be maculopapular, urticarial, angioedema, or an exfoliative dermatitis. [17] Cataracts can form, causing a permanent loss of vision in days to months of usage, and permanent deafness has also been reported. [17] [35] Other adverse effects reported include peripheral neuritis, agranulocytosis, and neutropaenia. [17] Negative effects on the central nervous system, cardiovascular system, and bone marrow can occur. [1] In animal studies, DNP acted as a teratogen, mutagen, and carcinogen and caused developmental and reproductive harm. [17] An unusually yellow coloring of the skin, mucous membranes, sclera, urine, stomach contents, and internal organs is an indication of DNP exposure, but does not occur in every case. [36] Contact with skin or inhalation can cause DNP poisoning. Symptoms are typically mild with dermal exposure, but inhalation can lead to systemic effects, the same way as oral exposure. [17]
Overdose is extremely dangerous; [17] cases reported to poison control centers had a 11.9 percent fatality rate between 2010 and 2020. [27] Although the largest number of overdose deaths occurred in the 1910s and 1920s when the chemical was in more widespread industrial use, [1] the substance's use as a dieting aid has caused a number of fatalities in the twenty-first century: [17] at least 50 overdose deaths were reported worldwide between 2010 and 2020. [27] Although the lowest published fatal ingested dose is 4.3 mg/kg, [17] [16] a typical overdose death occurs at a higher level of exposure, around 20-50 mg/kg. [1]
The first symptoms to appear are nausea, vomiting, abdominal pain, and perhaps diarrhea. [16] The typical overdose syndrome seen with DNP and other phenols is a combination of hyperthermia, tachycardia, diaphoresis, and tachypnoea. [16] [17] Because of the heat produced during uncoupling, DNP overdose will overpower the body's attempt to maintain thermal homeostasis and cause an uncontrolled, fatal rise in body temperature up to as high as 44 °C (111 °F). The disruption of metabolism also leads to the accumulation of potassium and phosphate, potentially contributing to toxicity. DNP can cause T wave and ST segment abnormalities; heart muscle, kidney, and liver damage have been found on autopsy. [16] [17] According to an analysis of United Kingdom and United States overdose cases, tachycardia, hyperpyrexia, acidosis, and agitation or confusion are independent predictors of overdose death. [37]
There is no antidote to DNP and management strategies are based on expert opinion and case studies. [17] Treatment for overdose is supportive, and often involves aggressive cooling using methods such as ice baths and intravenous fluids. [35] [17] Grundlingh et al. recommend administering activated charcoal if the patient presents within an hour of ingestion and using intravenous vasopressors or inotropes to control blood pressure if necessary. Intravenous methylthioninium chloride can treat methaemoglobinaemia. Benzodiazepines can help control seizures and dantrolene has been used in an attempt to control hyperthemia. [17] Cardiopulmonary resuscitation (CPR) has been used on people who died of DNP overdoses but has no known successful outcomes. [17]
During World War I, munitions workers in France fell ill and some died from DNP exposure. [38] Stanford University academic Maurice L. Tainter learned of DNP's effect in raising the metabolic rate and causing weight loss and pioneered its use as a weight loss drug. [1] [38] Although he was aware of DNP's narrow therapeutic index, Tainter tried the drugs on obese patients and published successful results in 1933; average weight loss was 20 pounds (9.1 kg) and most recipients did not report adverse effects. In 1934, Tainter estimated that at least 100,000 people had been treated with DNP in the United States during its first year on the market and there had been three reported fatalities connected to the drug. [38] [1] Tainter argued that DNP was highly effective in raising the metabolic rate (up to 50 percent) and avoided the negative circulatory effects of desiccated thyroid, another weight loss drug in use at the time. [38]
Other physicians were less optimistic about the adverse effects of DNP, and in 1935 the American Medical Association's Council on Chemistry and Pharmacy declined to list DNP in the New and Nonofficial Remedies on the grounds that its benefits did not exceed its risks to health. [38] Reports of cataracts forming during DNP usage administered by a physician appeared the same year; in 1936 an ophthalmologist based in San Francisco estimated that 2,500 American women had gone blind from DNP use. [38] Physician opinion turned against the drug, but many people bought direct-to-consumer preparations of DNP—marketed as a cosmetic rather than a drug to evade existing regulations. [38] [39]
DNP's risks were highlighted in the "Chamber of Horrors", an exhibit assembled by the Food and Drug Administration to explain the limitations of existing American drug regulations. In 1938, the Food, Drug, and Cosmetic Act increased the FDA's ability to regulate drugs. DNP was deemed so toxic as to be banned for human consumption and in 1940 the FDA reported that there was no evidence of continued sale for this purpose. [39] [38] Nevertheless, it continued to be used for weight loss. [35] William F. Loomis and Fritz Albert Lipmann discovered DNP's mechanism of action and reported it in a 1948 publication. [38]
Reports of its use increased in the twenty-first century after the drug became available on the Internet. [35]
DNP is banned for human consumption in many countries. [1] Because it has some legitimate uses, in many jurisdictions, DNP is legal to sell, but not for human consumption. [25] [40] [41] In Australia, all dinitrophenols were classified as Schedule 1 dangerous drugs in 1956. In February 2017, DNP was reclassified as Schedule 10, "Substances of such a danger to health as to warrant prohibition of sale, supply and use". [40] Since 1 October 2023, DNP has been classified as a regulated poison in the United Kingdom. [42] It is a prohibited substance (class F4) in Brazil. [43] In the United States, DNP is classified as an investigational new drug; it received orphan drug status for Huntington's disease. [44] DNP has been banned by the World Anti-Doping Association since 2015. [45]
Petróczi et al. recommend against campaigns informing people of the risks of DNP because it could increase use of the drug. [25] However, Sousa et al. argue that publicity campaigns in the United Kingdom in the early and mid-2010s reduced DNP usage. [1] In 2015, Interpol and the World Anti-Doping Agency released an orange notice warning of the dangers of DNP. [25]
In 1941, the Eastman Kodak Company, a bulk distributor of DNP, was investigated after some of its product was found in illegal diet pills. [39] Nicholas Bachynsky, a Texas physician, provided the drug to patients under the name "Mitcal". He was convicted of violating drug laws in 1986, but continued to work with DNP and was additionally convicted of fraud in 2008. [35] [17] In 2018, a seller in the United Kingdom was convicted of manslaughter for selling DNP for human consumption. The conviction was sent to retrial in 2020 by the English Court of Appeal, where the seller was, once again, convicted of gross negligence manslaughter. [46]
Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control excess body fat. These medications alter one of the fundamental processes of the human body, weight regulation, by: reducing appetite and consequently energy intake, increasing energy expenditure, redirecting nutrients from adipose to lean tissue, or interfering with the absorption of calories.
Levothyroxine, also known as L-thyroxine, is a synthetic form of the thyroid hormone thyroxine (T4). It is used to treat thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also be used to treat and prevent certain types of thyroid tumors. It is not indicated for weight loss. Levothyroxine is taken orally (by mouth) or given by intravenous injection. Levothyroxine has a half-life of 7.5 days when taken daily, so about six weeks is required for it to reach a steady level in the blood.
Thermogenic means tending to produce heat, and the term is commonly applied to drugs which increase heat through metabolic stimulation, or to microorganisms which create heat within organic waste. Approximately all enzymatic reaction in the human body is thermogenic, which gives rise to the basal metabolic rate.
25I-NBOMe, also known as Smiles, or N-Bomb, is a novel synthetic psychoactive substance with strong hallucinogenic properties, synthesized in 2003 for research purposes. Since 2010, it has circulated in the recreational drug scene, often misrepresented as LSD.
Dinoseb is a common industry name for 6-sec-butyl-2,4-dinitrophenol, a herbicide in the dinitrophenol family. It is a crystalline orange solid which does not readily dissolve in water. Dinoseb is banned as an herbicide in the European Union (EU) and the United States because of its toxicity.
Tricyclic antidepressant overdose is poisoning caused by excessive medication of the tricyclic antidepressant (TCA) type. Symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. If symptoms have not occurred within six hours of exposure they are unlikely to occur.
25B-NBOMe is a derivative of the phenethylamine psychedelic 2C-B, discovered in 2004 by Ralf Heim at the Free University of Berlin. It acts as a potent full agonist for the 5HT2A receptor. Duration of effects lasts about 3–10 hours, although the parent compound is rapidly cleared from the blood when used in the radiolabeled form in tracer doses. Recently, Custodio et al. (2019) evaluated the potential involvement of dysregulated dopaminergic system, neuroadaptation, and brain wave changes which may contribute to the rewarding and reinforcing properties of 25B-NBOMe in rodents.
N,N-Diallyltryptamine (DALT) is a tryptamine derivative which has been identified as a new psychoactive substance. It has been used as an intermediate in the preparation of radiolabeled diethyltryptamine.
25C-NBOMe is a psychedelic drug and derivative of the psychedelic phenethylamine 2C-C. 25C-NBOMe appeared on online vendor sites in 2010 but was not reported in the literature until 2011. It acts as a potent agonist of the 5-HT2A receptor, and has been studied in its 11C radiolabelled form as a potential ligand for mapping the distribution of 5-HT2A receptors in the brain, using positron emission tomography (PET). Multiple deaths have occurred from usage of 25C-NBOMe due to the ease of accidental overdose. The long-term toxic effects of the drug have not been researched.
Fish acute toxicity syndrome (FATS) is a set of common chemical and functional responses in fish resulting from a short-term, acute exposure to a lethal concentration of a toxicant, a chemical or material that can produce an unfavorable effect in a living organism. By definition, modes of action are characterized by FATS because the combination of common responses that represent each fish acute toxicity syndrome characterize an adverse biological effect. Therefore, toxicants that have the same mode of action elicit similar sets of responses in the organism and can be classified by the same fish acute toxicity syndrome.
25D-NBOMe is a derivative of the phenethylamine derived hallucinogen 2C-D. It acts in a similar manner to related compounds such as 25I-NBOMe, which is a potent agonist at the 5-HT2A receptor. 25D-NBOMe has been sold as a street drug since 2010 and produces similar effects in humans to related compounds such as 25I-NBOMe and 25C-NBOMe. It was banned as a Temporary Class Drug in the UK on 10 June 2013 after concerns about its recreational use.
25N-NBOMe is a derivative of the hallucinogen 2C-N. The pharmacological properties of 25N-NBOMe have not been described in the scientific literature, but it is believed to act in a similar manner to related compounds such as 25I-NBOMe and 25C-NBOMe, which are potent agonists at the 5HT2A receptor. 25N-NBOMe has been sold as a street drug and has only been described in the literature in terms of identification by forensic analysis.
25E-NBOMe is a derivative of the phenethylamine 2C-E. It acts in a similar manner to related compounds such as 25I-NBOMe, which are potent agonists at the 5-HT2A receptor. 25E-NBOMe has been sold as a drug and produces similar effects in humans to related compounds such as 25I-NBOMe and 25C-NBOMe.
Poisoning is the harmful effect which occurs when toxic substances are introduced into the body. The term "poisoning" is a derivative of poison, a term describing any chemical substance that may harm or kill a living organism upon ingestion. Poisoning can be brought on by swallowing, inhaling, injecting or absorbing toxins through the skin. Toxicology is the practice and study of symptoms, mechanisms, diagnoses, and treatments correlated to poisoning.
25G-NBOMe (NBOMe-2C-G) is a derivative of the phenethylamine hallucinogen 2C-G, which acts as a highly potent agonist for the human 5-HT2A receptor.
25H-NBOMe (NBOMe-2C-H) is a derivative of the phenethylamine hallucinogen 2C-H, which acts as a highly potent full agonist for the human 5-HT2A receptor.
25iP-NBOMe is a derivative of the phenethylamine hallucinogen 2C-iP, which acts as a highly potent agonist for the human 5-HT2A receptor.
The 25-NB (25x-NBx) series, sometimes alternatively referred to as the NBOMe compounds, is a family of serotonergic psychedelics. They are substituted phenethylamines and were derived from the 2C family. They act as selective agonists of the serotonin 5-HT2A receptor. The 25-NB family is unique relative to other classes of psychedelics in that they are, generally speaking, extremely potent and relatively selective for the 5-HT2A receptor. Use of NBOMe series drugs has caused many deaths and hospitalisations since the drugs popularisation in the 2010s. This is primarily due to their high potency, unpredictable pharmacokinetics, and sellers passing off the compounds in the series as LSD.
Nicholas Bachynsky is a Russian-born American former doctor and convicted fraudster. In the 1980s, he ran a weight loss clinic in Texas where he provided the unlicensed drug 2,4-Dinitrophenol (DNP) to patients under the name "Mitcal"; court filings reported that he had treated 14,000 people with the drug. Many reported adverse effects and at least one died. Bachynsky was convicted and fined for violating drug laws twice in 1986. Despite the convictions, he had earned over $8 million from his medical practice and continued to dispense DNP. In 2008, he was convicted of fraud for his role in a scheme to sell DNP. In 1988, he and some of his family and associates were charged with a variety of insurance fraud charges related to his DNP scheme. Bachynsky pled guilty to Part A of Count I, RICO, and Count 87, conspiracy to defraud the IRS in exchange for the prosecution dropping all other charges.
Energy expenditure, often estimated as the total daily energy expenditure (TDEE), is the amount of energy burned by the human body.