2,4-DiNitroPhenol [DNP]

Discussion in 'Steroid Forum' started by Heretic, Jan 10, 2004.

  1. TheRingloVale

    TheRingloVale Junior Member

    Would this be the place to put a DNP log, or should it have its own thread? I've been keeping one with the intent to share but I'm not familiar with the board and posting etiquette here.
     
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Separate ...
     
    FishnTom likes this.
  3. ironwill1951

    ironwill1951 Member

    I see on your profile that you will provide on line coaching that's scary,
    you have very little or no knowledge please keep you advice to yourself before you seriously hurt someone.

    don’t make stupid comments. front load to get saturation level to where it would be several days in because of its half-life. Stay away from chemicals you know nothing about/don’t do enough research on i guess. Have a spread sheet somewhere i’m going to post some more.

    edit: any other kid getting triggered by my post? should i not post my experience let me know in DM[/QUOTE]
     
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] 2,4 Dinitrophenol as Medicine

    In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950's to suggest that warfarin, a rat poison, could be repositioned into a breakthrough drug in humans to protect against strokes as a blood thinner. Yet it was approved in 1954 as Coumadin((R)) and has been prescribed to billions of patients as a standard of care.

    Similarly, no one can forget the horrific effects of thalidomide, prescribed or available without a prescription, as both a sleeping pill and "morning sickness" anti-nausea medication targeting pregnant women in the 1950's. The "thalidomide babies" became the case-in-point for the need of strict guidelines by the U.S. Food & Drug Administration (FDA) or full multi-species teratogenicity testing before drug approval. More recently it was found that thalidomide is useful in graft versus host disease, leprosy and resistant tuberculosis treatment, and as an anti-angiogenesis agent as a breakthrough drug for multiple myeloma (except for pregnant female patients).

    Decades of diabetes drug discovery research has historically focused on every possible angle, except, the energy-out side of the equation, namely, raising mitochondrial energy expenditure with chemical uncouplers. The idea of "social responsibility" allowed energy-in agents to be explored and the portfolio is robust with medicines of insulin sensitizers, insulin analogues, secretagogues, SGLT2 inhibitors, etc., but not energy-out medicines.

    The primary reason?

    It appeared unorthodox, to return to exploring a drug platform used in the 1930s in over 100,000 obese patients used for weight loss. This is over 80-years ago and prior to Dr Peter Mitchell explaining the mechanism of how mitochondrial uncouplers, like 2,4-dinitrophenol (DNP) even worked by three decades later in 1961. Although there is a clear application for metabolic disease, it was not until recently that this platform was explored for its merit at very low, weight-neutral doses, for treating insidious human illnesses and completely unrelated to weight reduction.

    It is known that mitochondrial uncouplers specifically target the entire organelle's physiology non-genomically. It has been known for years that many neuromuscular and neurodegenerative diseases are associated with overt production of reactive oxygen species (ROSs), a rise in isoprostanes (biomarker of mitochondrial ROSs in urine or blood) and poor calcium (Ca(2+)) handing. It has also been known that mitochondrial uncouplers lower ROS production and Ca(2+) overload.

    There is evidence that elevation of isoprostanes precedes disease onset, in Alzheimer's Disease (AD). It is also curious, why so many neurodegenerative diseases of known and unknown etiology start at mid-life or later, such as Multiple Sclerosis (MS), Huntington Disease (HD), AD, Parkinson Disease, and Amyotrophic Lateral Sclerosis (ALS).

    Is there a relationship to a buildup of mutations that are sequestered over time due to ROSs exceeding the rate of repair?

    If ROS production were managed, could disease onset due to aging be delayed or prevented?

    Is it possible that most, if not all neurodegenerative diseases are manifested through mitochondrial dysfunction?

    Although DNP, a historic mitochondrial uncoupler, was used in the 1930s at high doses for obesity in well over 100,000 humans, and so far, it has never been an FDA-approved drug. This review will focus on the application of using DNP, but now, repositioned as a potential disease-modifying drug for a legion of insidious diseases at much lower and paradoxically, weight neutral doses.

    DNP will be addressed as a treatment for "metabesity", an emerging term related to the global comorbidities associated with the over-nutritional phenotype; obesity, diabetes, nonalcoholic steatohepatitis (NASH), metabolic syndrome, cardiovascular disease, but including neurodegenerative disorders and accelerated aging. Some unexpected drug findings will be discussed, such as DNP's induction of neurotrophic growth factors involved in neuronal heath, learning and cognition.

    For the first time in 80's years, the FDA has granted (to Mitochon Pharmaceutical, Inc., Blue Bell, PA, USA) an open Investigational New Drug (IND) approval to begin rigorous clinical testing of DNP for safety and tolerability, including for the first ever, pharmacokinetic profiling in humans.

    Successful completion of Phase I clinical trial will open the door to explore the merits of DNP as a possible treatment of people with many truly unmet medical needs, including those suffering from HD, MS, PD, AD, ALS, Duchenne Muscular Dystrophy (DMD), and Traumatic Brain Injury (TBI).

    Geisler JG. 2,4 Dinitrophenol as Medicine. Cells 2019;8. 2,4 Dinitrophenol as Medicine
     
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  5. Kindlife

    Kindlife Member

    I think ppl talking about half lives of DNP, saturation doses, and frontloading massive doses of this drug need to think about the fact that everyones body dont act exactly the same and metabolize drugs at exactly the same rate like u can punch numbers in a calculator and come up with the exact measurment of how many mgs is in there system. One person might be able to take 1500mgs the first day and be fine dosing a smaller dose after that. But another person might die from that exact same protocol. Its irresponsible to post shit like that knowing its getting read by ppl that are new to the drug and might try what u are saying and wind up hurting themselves or even dying. Dnp already burns fat faster than anything else you're gonna do at a lower safe dose. Its a huge shortcut to your goal even at a safe dose. No need to risk your life to save a couple days time in reaching your target weight. New ppl to dnp should start at a low dose and stay at that same dose for a week b4 upping it and gauging how your body handles the drug. Then u can slowly raise it and experiment with what u can handle. Nobody's body is the same so dont think a chart or a calculator can tell u how your body is metabolizing a drug becuz it cant. Its a tool to use to help u along your way but its not an exact measurment of whats in u. Your levels could be much higher or much lower depending on your body and many other factors. Fear mongering and misinformation of this drug causes ppl to either never wanna touch this awesome drug but also causes ppl to be reckless and not respect the actual dangers that this drug poses. Basically all drugs can be helpful or harmful depending on how u use them. Be safe and educate yourselves with dnp so we dont lose access to this drug any more than we already have ppl.
     
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  6. FishnTom

    FishnTom Member

    Very true give this guy a cookie
     
  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] [DNP] Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases

    However, it is possible to create compounds that will specifically, directly, and safely increase hepatic mitochondrial energy expenditure. We previously demonstrated the efficacy of low doses of the mitochondrial protonophore, 2,4-dinitrophenol (DNP), in preventing steatosis in high-fat-fed rats, with decreased PKCε activation and improved hepatic insulin signaling and hepatic insulin action (Samuel et al., 2004).

    Though DNP has been used clinically in the past, this compound is not safe for clinical use due to the low therapeutic index. If DNP is modified with a methyl-ester (ME), it remains inactive until activated within hepatocytes. This increases the therapeutic index of DNP-ME 50-fold over DNP.

    DNP-ME increased hepatic mitochondrial fat oxidation by ∼60% and reversed hypertriglyceridemia, hepatic and peripheral insulin resistance, and hyperglycemia in rat models of NAFLD and T2D (Perry et al., 2013). DNP-ME did not alter cellular energy charge, nor did it lead to activation of AMPK; its actions are likely due purely to the induced energy inefficiency of the mitochondria exclusively in liver.

    Furthermore, correction of liver and muscle insulin resistance was associated with marked reductions in liver and skeletal muscle DAG content with decreased activation of PKCε and PKCθ, respectively. The latter improvements in muscle DAG-PKCθ activity could be attributed to DNP-ME increased in hepatic fat oxidation, leading to reduced VLDL production, reduced plasma triglycerides, and decreased fat delivery to skeletal muscle. Importantly, these improvements occurred independently of any changes in body weight, inflammatory mediators, FGF-21, adiponectin, or hepatic ceramide content (Perry et al., 2013).

    Similar effects were seen with a second liver-targeted mitochondrial uncoupling agent, controlled release mitochondrial protonophore (CRMP) (Perry et al., 2015b). Combining DNP into a cellulose-based matrix extends the time required for absorption, resulting in relatively stable plasma DNP concentrations after oral administration. CRMP increases the therapeutic index by 500-fold and, as with DNP, lowers hepatic and muscle lipid (DAG) content and improves insulin hepatic and peripheral sensitivity in numerous rodent models of NAFLD/NASH (Perry et al., 2015b).

    While CRMP is not “liver specific” by design, the first-pass hepatic uptake largely confines its actions to the liver. CRMP increased the rate of hepatic tricarboxylic cycle flux without changing whole-body energy balance or mitochondrial activity in other tissues. Like DNP-ME, the reductions in plasma triglyceride and improvement in skeletal muscle activity were attributed to CRMP-induced increases in hepatic mitochondrial fatty acid oxidation, resulting in decreased VLDL production and hypertriglyceridemia and reduced delivery and uptake of fat by the skeletal muscle. In rats fed an MCD diet, CRMP treatment reduced hepatic inflammation and reversed hepatic fibrosis.

    CRMP has also recently been shown to reverse hepatic steatosis and hepatic and peripheral insulin resistance in an A-ZIP/F1 mouse model of severe lipodystrophy (Abulizi et al., 2017). CRMP also decreased several markers of liver inflammation and the unfolded protein response in this lipodystrophic mouse. Furthermore, CRMP, like DNP-ME, reversed hepatic insulin resistance and diabetes with reductions in hepatic DAG-PKCε activity and hepatic acetyl-CoA content, offering further support for the roles of these metabolites in causing hepatic insulin resistance and increased hepatic gluconeogenesis, respectively, in T2D.

    Taken together, these studies offer proof of concept in support of the development of novel liver-targeted mitochondrial uncoupling agents for the treatment of NAFLD, NASH, and T2D.

    Samuel VT, Shulman GI. Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases. Cell metabolism 2018;27:22-41. http://www.sciencedirect.com/science/article/pii/S1550413117304874
     
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  8. Kindlife

    Kindlife Member

    Curious if anyone knows anything about niclosamide ethanolamine. Its a mitochondrial uncoupler used in studies as a cure for type 2 diabetes and other similar things DNP is used for. But ive read its supposed to be much safer and more effective but i haven't seen any studies on weight loss but im thinking that could possibly be an effect of it as well. Just wondering if anyone has any knowledge about it they can share as it sounds interesting. if we can find something that works as good as dnp for fat loss without or at least less dangers would be a good thing for a lot of ppl.
     
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  9. Kike

    Kike Junior Member

    Very very benefical thank you. Bit of a read lol but much appreciated
     
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  10. FishnTom

    FishnTom Member

    She didnt bother reading the directions
     
  11. 88GENERAL88

    88GENERAL88 Member

    “Killed literally 6weeks of diet off a show?”
    you could have killed yourself and then, I wonder how you would have placed then. I know that this is where people are suppose to come and feel comfortable taking about the experience, and/or about asking questions, however, I feel there is an exception to that rule. Which is dnp, just because you managed to cheat death by using a method that your mind was able to make sense of. Dnp use is not the same the use of AAS. Because of the hightened risk involved(death) it need to be treated with a different level of finesse, respect, and responsibility. Any disregard for those things by an individual, tells me, that person is not ready to deal with the consequence, shall any arise.
     
    Last edited: Apr 14, 2019
  12. rbj

    rbj Junior Member

    30+ shows later, here i am. you mad?
     
  13. 88GENERAL88

    88GENERAL88 Member

    No not at all, I don’t have a beef with you, but I do agree with what everyone has said, all it takes is for one person, to come on here, read about your irresponsible attempt at winning a contest, because they thought they can gamble with your method, and they end up dead. The fact that You remain so cavalier about it is really sad. No one said that you were an idiot, at least not in the beginning, they are all saying that the fact that you went over and above to post irresponsible activity out in the open, is stupid.
     
  14. rbj

    rbj Junior Member

    Sorry, do you want a hug now or later friend?
     
  15. ParagonLabs

    ParagonLabs Junior Member

    Have not tried this compound yet but doing research maybe this summer!
     
    FishnTom likes this.
  16. FiEnD

    FiEnD Member

    Paragon BJJ too?
     
  17. FishnTom

    FishnTom Member

    U wanna do this during the winter or befor spring buddy u will be miserable during summer with this compound
     
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  18. Holidaypay

    Holidaypay Member

    @rbj people aren't trying to be a dick u have to realize that young kids could come here an see what u did an think its ok an safe especially when u brag about ur 30+ shows therw are young men out here who will see this an think its ok an its not ur words carry consequences an u should be a little more considerate when u post dangerous things in the most famous steroid forum in the world...its called harm reduction for a reason there is always bop tho
     
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  19. Dr JIM

    Dr JIM Member

    Another rodent DNP study, knowing the difference bt human and rodent hepatic metabolism extrapolation to humans is ill advised in the absence of clinical trials.

    Jim
     
  20. Dr JIM

    Dr JIM Member

    Let see some pics and all your trophies, lol!
     
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