# Medicinal uses of poison dart frog venom



## wmarkjones

I was curious to learn from you all about what you know about the medicinal uses of poison-dart frog venom. In the web article, "Poison Dart Frog" (at Poison Dart Frogs, Poison Dart Frog Pictures, Poison Dart Frog Facts - National Geographic), they said, "The medical research community has been exploring possible medicinal uses for some poison dart frog venom. They have already developed a synthetic version of one compound that shows promise as a painkiller." This is especially interesting to me, since my late wife died of ovarian cancer, and a common treatment for that disease is the intravenous infusion of Taxol, a compound extracted from the yew tree. This extraction and treatment process seems to be a possible parallel to the use of dart-frog venom referenced in this article.

Are any of you aware of the developments in this research? Are any of you involved in this research? If so, what is your experience in this area? Other questions that naturally occur to me are also:

- Is a chemical process documented yet whereby the pain-killing toxin can be manufactured without the use of a biological host, such as dart-frogs?
- Can the dart-frog community be a part of this research?
- What are the pain-killing mechanisms of the toxin?
- Is the dart-frog's resistance to the toxin reproducible in other organisms (as is observed in leimadophis epinephelus) -- i.e. if a biological host is needed for the production of the compound en masse, can another, less sensitive (non-endangered) organism be used instead of dart-frogs?

Thanks,

Mark


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## Julio

there was a pharmaceudical company about 10 years ago that published an article on a pain killer they produced from Tricolors that is 200xs stronger then morphine, not sure what ever happened with that.


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## D3monic

200x's stronger than Morphine? Wow! Hey I feel no pain...ohh wait thats because im Dead!


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## Julio

hahahah, well that is what the article read.


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## Julio

Powerful Cancer Pain Killer from Ecaudoran Frog


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## wmarkjones

Julio said:


> Powerful Cancer Pain Killer from Ecaudoran Frog


Julio,

Thanks for the link -- the article was interesting, but it raised more questions, specifically:

Is the compound ABT-594 ("epibatidine") being evaluated by the FDA? I couldn't find any references to it on fda.gov under either of the compound names. The paper you referenced (http://my.eurorscg.com/unprotected/...mavitae 2002, Abbott Laboratories, Mar 02.pdf) says, "ABT-594 has the potential to create a new market for the treatment of pain, replacing the use of morphine, provided it can prove a clinical profile with improved efficacy, and most importantly, reduced side effects when compared with its opioid rivals." It goes on to say, "Should Abbott successfully demonstrate superior efficacy to morphine with a significantly reduced side effect profile, the market for the new drug would be very large. Datamonitor estimates that opioid and opioid combination therapies were worth almost $6 billion globally in 2001, highlighting the market potential for Abbott’s drug. However, Abbott has yet to release significant results from clinical trials, and will need to produce convincing data if it is to fulfill the drug’s potential. The project carries a high risk, but has the potential of high rewards assuming it comes to market after 2006." Do you know of any recent developments regarding FDA's evaluation of ABT-594, if any such evaluation is underway?

FYI, another interesting article about this compound is at http://www.chm.bris.ac.uk/motm/abt/abt.html.

Thanks again,

Mark


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## D3monic

ABT - 594


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## Julio

that is not the article i am refering to, it was an article that was given way back at the first held IAD. I am sure we are way off before this stuff gets any approval from the FDA


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## wmarkjones

Julio said:


> that is not the article i am refering to, it was an article that was given way back at the first held IAD. I am sure we are way off before this stuff gets any approval from the FDA


Thanks anyway. I appreciate the feedback. I guess I'll send some correspondence to the FDA and to Abbott for further info.

Mark


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## Julio

anytime, you might also wanna contact Dr. Wright out in Arizona and see if he has any info on the subject.


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## BlueRidge

Julio said:


> that is not the article i am refering to, it was an article that was given way back at the first held IAD. I am sure we are way off before this stuff gets any approval from the FDA


Aw....the FDA is such a crock of (blank)! I'm a believer that there are untold medical treatments hidden in the rainforests and known only to the local tribes and that these cures will possibly never be found because of the FDA. Aids came from the rainforest and it's cure is there as well, but think about it. The FDA would never approve a treatment from a plant in the Amazon without millions of dollars of research and pocket linings before it hits the market.

I'm sorry, this is a sore spot for me. My wife is a medical professional and she tells me the horror stories of ins companies and how the pharmaceutical reps wooo the doctors to get them to push their drugs, etc.

I would not doubt one bit, that with technology today, a lab could synthesize the toxins and create pain killers that were not addictive and worked better. I honestly don't think the FDA should be involved at all.


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## Catfur

A thread from before you all's time:

http://www.dendroboard.com/forum/science-conservation/17054-curious-question-epibatidine.html

Executive summary: this line of research is no longer being pursued, as they haven't been able to find a compound that isn't also too toxic for use as a medicine.


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## earthfrog

JaredJ said:


> Aw....the FDA is such a crock of (blank)! I'm a believer that there are untold medical treatments hidden in the rainforests and known only to the local tribes and that these cures will possibly never be found because of the FDA. Aids came from the rainforest and it's cure is there as well, but think about it. The FDA would never approve a treatment from a plant in the Amazon without millions of dollars of research and pocket linings before it hits the market.
> 
> I'm sorry, this is a sore spot for me. My wife is a medical professional and she tells me the horror stories of ins companies and how the pharmaceutical reps wooo the doctors to get them to push their drugs, etc.
> 
> I would not doubt one bit, that with technology today, a lab could synthesize the toxins and create pain killers that were not addictive and worked better. I honestly don't think the FDA should be involved at all.


I think if there were more objective agencies doing this work---third party regulatory companies, like we have for our credit cards/loans---then we would get more help more quickly in situations like these. I have witnessed this 'drug pandering' in clinics too---in exchange for free lunch, the doctors feel good about a drug and pass it off to others, testing it on them in the meantime. The assumption is that the drug is good for you, and the doctor highly recommends it, when in fact he just got some free samples during lunch and has done ZILCH reading about its safety/efficacy (hence the huge Vioxx issue). 

However, I would be more interested to hear if there are any updates on this---with a 14% chance of ovarian cancer myself, I'm sure I'm not the only one a bit curious about such a use for this drug!
There is similar research underway for the use of PDF toxins to treat drug-resistant infections---I hope it moves along faster since I hear of too many infections these days in perfectly sound people...


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## earthfrog

Catfur said:


> A thread from before you all's time:
> 
> http://www.dendroboard.com/forum/science-conservation/17054-curious-question-epibatidine.html
> 
> Executive summary: this line of research is no longer being pursued, as they haven't been able to find a compound that isn't also too toxic for use as a medicine.



That's a real shame. 
I heard of another cancer treatment where they designed the molecule to be too large to get into healthy blood vessels to destroy good tissue---human trials were in the making over a year ago. It was based on a plant compound that was normally lethal, but they bound it to a harmless sugar and created a molecule that was too large to harm normal human tissue. In about three months (I think) they greatly diminished the size of lung tumors that were otherwise untreatable, with no visible/harmful effect on the test subject. 
Waiting for that one to come around...
I guess they need to keep hacking away at this.


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## earthfrog

D3monic said:


> ABT - 594





Blort said:


> Bill,
> 
> I hear you on bio-piracy issues and such. Those are topics worthy of their own thread some day.
> 
> Part of what I understood the hype was about revolved around addiction to epibatidine with the drug being touted as non non-addictive alternative to morphine. Was that totally overblown and do you anticipate that much of the buzz around epibatidine is likely to fade?
> 
> Marcos





elmoisfive said:


> Marcos,
> 
> Yes the speculation is that one can produce non-addictive nicotinic agents that would function for pain, cognition, etc. Preclinically, results with ABT-594 were suggestive that it did not produce dependency in rat studies. However, these types of experiments are difficult to extrapolate to the human setting and ABT-594 did not progress far enough in clinical testing to give the hypothesis a good test.
> 
> Varenicline as mentioned before has been shown to have efficacy in the absence of dependency (addiction). However, there is some speculation this may be due to the fact that it is a partial as opposed to full agonist at the nicotinic acetylcholine receptor. A partial agonist activates a receptor but only produces a partial physiological response compared to a full agonist.
> 
> Epibatidine and ABT-594 are full agonists and it is extremely difficult although not impossible to 'dial' partial agonism into a structural class. So if the partial agonist theory pans out, it will be one more strike against those compounds. On the other hand, there is too little data to draw a conclusion at this point.
> 
> I think that the buzz surrounding the opportunities of selective nicotinic agents will continue to be with us and in time the field will produce more drugs. How Epibatidine continues to be tied to this situation will likely be more due to popular imagination as opposed to therapeutic utility.
> 
> Bill


These are from the older thread Clayton posted---I hope to see more from this idea in the future.


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## BlueRidge

earthfrog said:


> I have witnessed this 'drug pandering' in clinics too---in exchange for free lunch, the doctors feel good about a drug and pass it off to others, testing it on them in the meantime.


Free lunch? Hell, the drug reps here give Dr's vacations, weeks in timeshares, you name it. Lunch is usually just to get into the office. LOL, at my wife's office the drug reps usually cater lunch in at least once a week and we're not talking Olive Garden or Panera. It's not cheap.

It's really a shame that they focus more on money than helping patients.


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## wmarkjones

Julio said:


> anytime, you might also wanna contact Dr. Wright out in Arizona and see if he has any info on the subject.


Julio,

Thanks for the reference. I sent him the following note (to [email protected]). I'll relay his response if I hear back.

----------------------------------

Dr. Wright,

I'm writing to inquire about your knowledge of the research surrounding ABT-594 (epibatidine). I have a few questions:

- Is this being evaluated by the FDA?
- Are you aware of where Abbott is in their research?
- Is a process documented whereby the pain-killing toxin can be manufactured without the use of a biological host, such as dart-frogs?
- Can the dart-frog community be a part of this research?
- What are the pain-killing mechanisms of the toxin?
- Is the dart-frog's resistance to the toxin reproducible in other organisms (as is observed in leimadophis epinephelus) -- i.e. if a biological host is needed for the production of the compound en masse, can another, less sensitive (non-endangered) organism be used instead of dart-frogs?
- Do you know any particulars regarding how a typical dosage in a human subject affects cognitive function?

I would appreciate hearing back from you on this if you have the time.

Thanks,

Mark Jones


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## Jules2

Hi there
I just joined this forum because I am also interested in using the 'poison' of the phantasmal poison frog for chronic pain. I believe it has great potential in this area of therapy. Does anyone know of studies about the effectiveness of this very powerful pain killer? 

Some may find this also interesting-this frog was shown to me during an ayahuausca ceremony as a powerful healer. I work with chronic pain patients so I'm very excited about the possibility of a new medication which is not an opiate.


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## Jules2

I am a counsellor working with chronic pain patients and I am also very interested in this compound as a possible alternative to surgery or opiates. If anyone knows of further research on this topic, please let me know.

To answer one of your questions perhaps- I think isolating the compound and making it synthetically would be the best way to proceed rather than using live frogs. Its seems this compound works in unique ways on the nervous system which in lesser doses could be beneficial for chronic pain.

When the pain is due to 'mechanical' causes, then this so called poison could be extremely beneficial especially if it isn't addictive or doesn't have the side effects of other known pain killers.

I'm wondering why pharmaceuticals haven't jumped on board with this??? Too engaged in known pain killers such as opiates which are relatively cheap to produce and have research to back the product?

Just wondering! Any researchers out there interested in the same things?


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## Tzunu'un

Epibatidine causes dangerous toxic side effects and further development of it stopped a while ago..


Tebanicline or abt-594 is the the second generation chemical derivative of epibatidine that made it as far as Phase II clinical trials. Although less toxic than epibatidine, tebanicline also showed unacceptable side effects (gastrointestinal).

Natural products are often good for finding new pharmacophores (chemical structure templates with pharmacologic action) not found by traditional screening of synthetic chemical libraries, but most of the time the natural products themselves aren't useful in therapy as is and need to be further developed / modifications explored by traditional medicinal chemistry.

The Wikipedia entry points to some interest in finding new neural nicotinic acetylcholine receptor agonists.

A simple Google search will yield the info that you need / are specifically looking for.
https://en.wikipedia.org/wiki/Tebanicline

also search neural nicotinic acetylcholine receptor agonists in regard to analgesia / neuropathic pain.


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## darterfrog4774

Do any of you guys watch Last Week Tonight? They had an episode on pharmaceutical reps on their Youtube channel.


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## easternversant

Jules2 said:


> Some may find this also interesting-this frog was shown to me during an ayahuausca ceremony as a powerful healer. I work with chronic pain patients so I'm very excited about the possibility of a new medication which is not an opiate.


Ayahuasca eh? Nothing sounds worse to me than those 'ceremonies.' l can't tell you how much I don't want to hallucinate, get extraordinarily ill and puke my guts out--all while being eaten alive by insects in the forest. 

If you were interested in it as a medication for your patients, maybe you should check on FDA approved, legal drugs? 

But to sort of answer your question, in parts of South America some people do use poison frogs medicinally. As far as I can tell they catch _Ranitomeya_ or _Epipedobates_ frogs (I sort of suspect it is the later, but the description could have been either), agitate them, poke two holes into someone's arm, and then run either the frog or its secretions into these holes. I've heard good things about it. But the same people who have told me it was good described their symptoms as initial intense pain, periods of tingling and numbness, spikes in heart rate and blood pressure, etc. So, in conclusion, it all appears to be a load of hogwash. On a thread that has been dead for 5 years.


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