2,4-Dinitrophenol (DNP), C6H4N2O5, is a cellular metabolic poison. It uncouples oxidative phosphorylation by carrying protons across the mitochondrial membrane, leading to a rapid consumption of energy without generation of ATP.
Dinitrophenols as a class of compounds, of which there are six members, do not occur naturally but are all manufactured compounds.
2,4-Dinitrophenol is a yellow, crystalline solid that has a sweet, musty odor. It sublimes when carefully heated and is volatile with steam. It is soluble in water (sparingly) (its crystalline sodium salts are also soluble in water), cold water (sparingly), ethyl acetate, acetone, chloroform, pyridine, carbon tetrachloride, toluene, alcohol, benzene, and aqueous alkaline solutions (Merck, 1989). It forms explosive salts with alkalies and ammonia, and emits toxic fumes of nitrogen oxides when heated to decomposition (Sax, 1989). It is incompatible with heavy metals and their compounds.
Some advocates of the drug advise people to take doses of 5-8 mg/kg daily. It's commonly advised, however, that the dose be slowly titrated according to personal tolerance, which varies greatly.
There is limited and conflicting data on the pharmacokinetics of DNP in humans. The EPA states that "Data on the elimination kinetics of the dinitrophenols or their metabolic products in humans were not found. The ATSDR's Toxicological Profile for Dinitrophenols also states that "No studies were located regarding distribution in humans after oral exposure to 2,4-DNP. Limited information is available regarding distribution in animals after oral exposure to 2,4-DNP." However, they do state that "Elimination from the body appears to be rapid, except possibly in cases of compromised liver function. This conincides with a review in the NEJM on the biological actions of dinitrophenol, which stated that "Judging from the metabolic response, DNP appears to be eliminated entirely in three or four days; in the presence of liver or kidney damage it is possible that the drug will be retained over a longer period. Oddly, more recent papers give an array of possible half-lives, ranging from 3 hours, to 5-14 days. Other recent papers maintain that the half-life in humans is unknown.
In a study on mice, a lethal dose of 35 mg/kg decreased to 5 mg/kg body weight when the environmental temperature was raised to 39° C (102.2° F). As the ambient temperature increases, so does the risk of overheating. People who use increased ambient temperatures for weight-loss, such as wrestlers and runners, are potentially at greater risk of overdose.
Although further investigation is needed, dinitrophenol-induced hyperthermia has been successfully resolved with dantrolene administration. "Dinitrophenol uncouples oxidative phosphorylation, causes release of calcium from mitochondrial stores and prevents calcium re-uptake. This leads to free intracellular calcium and causes muscle contraction and hyperthermia. Dantrolene inhibits calcium release from the sarcoplasmic reticulum which reduces intracellular calcium. The resulting muscle relaxation allows heat dissipation. There is little risk to dantrolene administration. Since dantrolene may be effective in reducing hyperthermia caused by agents that inhibit oxidative phosphorylation, early administration may improve outcome."
While DNP itself is considered by many to be too risky for human use, its mechanism of action remains under investigation as a potential approach for treating obesity. Currently, research is being conducted on uncoupling proteins naturally found in humans.
However the effects of DNP on anaerobic micro-organisms are still largely undetermined. Some studies suggest there is anaerobic toxicity due to a reduced methane production.