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Medicinal uses of poison dart frog venom

17K views 21 replies 10 participants last post by  easternversant 
#1 ·
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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#6 · (Edited)
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
 
#15 ·
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
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.
 
#17 ·
Julio,

Thanks for the reference. I sent him the following note (to info@azeah.com). 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
 
#12 · (Edited)
#14 ·
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.
 
#18 ·
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.
 
#22 ·
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.
 
#19 ·
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?
 
#20 ·
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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