B.R.S.M. To strive, to seek, to find and not to give a yield

21Oct/126

Drugs I Shan’t Be Taking This Week 1: 2,4-Dinitrophenol

I was saddened and surprised today to read this story on the BBC News website about a young man who died by overdosing on 2,4-dinitrophenol. Huh? Now, perhaps on account of my long hair and somewhat dishevelled appearance, I get offered a lot of drugs, but this isn't something I've ever heard hawked on street corners. It turns out that despite previous uses as a detonator and pesticide it's apparently quite popular among bodybuilders as a weight loss drug, something the FDA found it to be unsafe for back in 1938. Which is really something as 'safe' had a whole different meaning back then; hell, the 1948 the Nobel Prize for Medicine was awarded to Paul Müller for his discovery of 'wonder' pesticide DDT. But how does 2,4-dinitrophenol work? Well, here's a mechanism of action I wouldn't have guessed:

"DNP acts as a protonophore, allowing protons to leak across the inner mitochondrial membrane and thus bypass ATP synthase. This makes ATP energy production less efficient. In effect, part of the energy that is normally produced from cellular respiration is wasted as heat. 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 meet energy demands. DNP is probably the best known agent for uncoupling oxidative phosphorylation."

Well, that sounds tempting! So, for a slightly higher basal metabolism you get a permanent fever, sweats and insomnia! Surprisingly, to me at least, mitochondrial uncoupling appears to be considered a valid approach for the development of anti-obesity drugs, despite these unavoidable side effects. The problem with using 2,4-dinitrophenol for this purpose is that the therapeutic index is very small, and overheating is quite easy even using a 'safe' dose, causing all kinds of problems. I read a few accounts of people's experiences with the drug online, and most of them concluded that taking 2,4-DNP was far more unpleasant than good old fashioned dieting. As Samuel Goldwyn once said, "gentlemen, include me out".

 

 

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  1. There is a bit more potent insecticide version – 4,6-dinitro-orthocresol . That one is cumulative and has a threshold above which it becomes suddenly and unpredictably lethal. It was used for spraying fruit trees so the exposure (including yellow skin discoloration and bitter taste) was common in orchard workers. Hot weather and sweating apparently increased the skin absorption…

    For a charming study see

    ” POISONING BY DINITRO- ORTHO-CRESOL – SOME OBSERVATIONS ON THE EFFECTS OF DINITRO-ORTHO-CRESOL ADMINISTERED BY MOUTH TO HUMAN VOLUNTEERS”

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2069381/pdf/brmedj03501-0042.pdf

    the study is followed by another article named “POISONING BY DINITRO- ORTHO-CRESOL – REPORT OF EIGHT FATAL CASES OCCURRING IN GREAT BRITAIN”

    Also there is rodenticide version that is taste-free and colorless, called bromethalin. It selectively accumulates in brain; turns out decoupling mitochondria in CNS gives you a ginormous case of brain edema and horrible death.

  2. DNP gets a bad rep by the sedate and cautious, but it has a long history of use. The hyperthermia is expected and wanted by informed users, and can be planned for. Seriously, how are you to burn off a lot of fat in a short period of time without getting a little hot. At least DNP is probably safer than trying to induce serotonin syndrome for the same purpose. What else will do the job?

    This isn’t for dieting, it is for crash fat reduction.

  3. The same mode of action works for bacteria too, and phenols have been used as antimicrobials for quite a while. The most successful analogue was hexachlorophene, which was mostly discontinued in the 70’s, after it was found to both paralyze lab annimals and accumulate in the tissue of… babies.

  4. I know from experience that body-builders represent the least informed users of ‘grey market’ drugs. This is a group of people who considered sharing needles to be safe because they ‘merely’ go into muscle and not into veins!

  5. I’ve always found people named Sean usually speak for a group of people without actually having any affiliation with them. If you weren’t indulged in your own satisfaction of self, you could stand aside and hear how retarded you sound.

    DrSnowboard…did you read the study? The study you posted was about DNOC not DNP. Similar structure and mechanism of action. Almost no one is going to feel or even die from 75mg of DNP. How much do you need to start feeling hot? Oh, you probably haven’t been exposed to it.

    You guys are a sad group. Bunch of desk jockeys who hide behind studies. All these idiots on these sites back up their opinion with studies. Get out in the real world and observe actual effects on actual people.

    Patrick Sweetman is the only one site a logical statement. I can tell he has real world exposure to DNP. He didn’t just read that shit online. But his opposition is met with a copy and paste of a study with little relevance.


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