- Captopril (CAPOTEN), an ACE inhibitor derived from the venom of the jararaca pit viper (Bothrops jararaca).
- Enalapril (VASOTEC), another angiotensin-converting enzyme (ACE) inhibitor drug made from the venom of the jararaca pit viper snake (Bothrops jararaca).
- Exenatide (BYETTA), a glucagon-like peptide-1 receptor agonist drug made from the venom of the Gila monster lizard (Heloderma suspectum).
- Exenatide (BYDUREON), an extended release version of BYETTA also made from the venom of the Gila monster lizard (Heloderma suspectum).
- Ziconotide (PRIALT), a Cav2.2 channel antagonist drug made from the venom of the magical cone marine snail (Conus magus).
- Bivalirudin (ANGIOMAX), a reversible direct thrombin inhibitor drug made from the venom of the European medicinal leech (Hirudo medicinalis).
- Lepirudin (REFLUDAN), a drug that binds irreversibly to thrombin and that is also made from the venom of the European medicinal leech (Hirudo medicinalis).(Huff, E.)
These are just some of the many drugs that have been made using extracts of animal venom and toxins. Since the beginning of time, humans have used animal venom as medicine, and we continue to do that today. Although this has been happening for centuries, new venom-based drugs are still discovered almost every year.. The toxins of these animals are very important to the development of medicine. We continuously treat many conditions using these toxins and discover more and more fascinating things about their biology. In this article I will be delving deeper into the field of animal venoms and toxins used in pharmaceutical drugs and medicine.
Approved drugs
There are 11 total animal toxin based molecules that are approved for medical use. From cone snails, we have the molecule ziconotide. From lizards, there is exenatide and lixisenatide. From leeches are the molecules bivalirudin and desirudin. Finally, from snakes we have captopril, enalapril, tirofiban, eptifibatide, batroxobin, and cobratide.
Some approved drugs, used in medicine, that contain these animals toxins include:
Batroxobin:
Defibrase; Obtained from a Brazilian lancehead snake/Bothrops moojeni. It is used for acute cerebral infarction, unspecific angina pectoris, and sudden deafness.
Plateltex-Act; Obtained from a common lancehead snake/Bothrops atrox. Used for gelification of blood for topical applications.
Bee venom therapy(Apitox): Obtained from honeybees/Apis mellifera. Employed for pain associated with osteoarthritis and multiple sclerosis.
Bivalirudin (Angiomax): Obtained from European medicinal leech/Hirudo medicinalis. Used as an anticoagulant in percutaneous coronary intervention.
Cobratide(Ketongning cobrotoxin): Obtained from a Chinese cobra/Naja naja atra. Used for chronic arthralgia, sciatica, and neuropathic headaches.
Cosmetic uses
The use of venom and toxins as cosmeceuticals has already been quite successful. Botox, also known as Botulinum toxin, which is isolated from the Clostridium botulinum bacteria, has been a pretty popular toxin used globally since 1989. The toxin essentially causes mild muscle paralysis, giving a smoother non-wrinkled effect to the skin. 3 billion dollars is now constantly being generated by this drug annually. Botulinum toxin is not the only toxin used for anti-aging purposes. Tripeptide, derived from Tropidolaemus wagleri snake venom, is also being used as a serum to reduce wrinkles. Apis mellifera L. honeybees are also getting venom extracted from them to be used in facial serums that are believed to help with wrinkles caused by UV damage. Argiope lobata spider venom is also being used for skin and teeth whitening.
Potential toxins
Natriuretic peptide, specifically dendroaspis natriuretic peptide (DNP), was acquired from the Eastern green mamba snake (Dendroaspis angusticeps). DNP has many structural similarities to human natriuretic peptides, and greatly helps in cardiac unloading. Due to its nature it is believed that it’ll become extremely helpful to patients with heart failure. Many clinical trials were conducted with this peptide and they showed great results in patients with stable, chronic heart failure. Due to these trials, natriuretic peptides, specifically atrial natriuretic peptide (ANP), ventricular natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are currently being tested for the treatment of heart failure.
Vc1.1, an α-conotoxin (ACV1) derived from Conus victoriae, is presently being tested for its analgesic components. The α-conotoxins were tested on a group of participants who showed no negative side effects after administration. The ACV1 was then tested again for diabetic peripheral neuropathic pain and showed little effectiveness, ultimately leading to its discontinuation. This didn’t stop us from continuing testing on α-conotoxins though. Successes, such as with ziconotide from Conus magus, shows us how helpful marine creatures’ toxins and venoms could be as pharmaceutical therapeutics.
The vampire bat(Desmodus rotundus), is another animal that is perceived to have venom that could be useful to us. With the isolation of a 441 amino acid fibrin-dependent plasminogen activator found in their venom, blood clots can be effectively broken down. The venom was tested for its potential in treating ischemic strokes, but the clinical trials were ineffective, causing it to be discontinued later on.
Challenges
One challenge that arises from using animal toxins and venom is, for animals that are rarer or smaller, it is hard to get enough venom to do research on or even use for making drugs. An example of this is the amount of venom that is acquired from the Cupiennius salei spider is only 10 microliters, as compared to the snake Lachesis muta muta where we get 200-400 milligram of toxins and venom. This is one reason as to why some animal toxins are used in drug research and production more often than others.
The toxins and venoms collected may not meet all the requirements to be used in therapeutic applications. It is necessary to collect enough of the toxins. This can vary from species to species. It is oftentimes a challenge to figure out how to separate the needed biological components in the toxins from other things that have been extracted with it.
Before any of the drugs made with the toxins can be approved for use and mass produced, there needs to be multiple clinical trials done. These trials are very critical and allow us to collect important data for future use and improvement. This also comes with its limitations since vulnerable populations, such as children, pregnant women, and the elderly cannot be used in the trials. The toxins in these drugs may react very differently to different groups of people, so not being able to conduct the trials on certain people definitely hinders how far the drugs can go and how much it can be improved.
Past problems
Ximelagatran, a peptide, was discontinued in 2006. When the peptide was used in clinical trials, the majority of the participants had no negative side effects. However, a small number of participants began experiencing elevated liver enzyme levels which could potentially lead to damages within the liver. Due to that, ximelagatran was rejected to be used as a pharmaceutical drug.
Agkisacutacin was previously used in clinical trials to help prevent excessive bleeding during and after surgery, but due to some complications, such as severe allergic reactions, the tests were discontinued.
Pexiganan, found from the skin of the Xenopus laevis frog, showed potential in treating infected foot ulcers in diabetic patients. In 1999 pexiganan was denied to be used as treatment for there wasn’t any evidence of it being better than the current medicines we have for the particular infections it treats.
Conclusion
Venom and toxins from animals have been used for a long time in the field of medicine. Even though there are many that may not be of use, there are still many more that show promising results when tested. If we continue to test these toxins there are large possibilities that we would find the treatments and solutions to many illnesses that constantly plague our lives. The treatments for conditions such as arthritis, asthma, cancer, chronic pain, infections, and cardiovascular diseases can very likely be discovered and created using animal toxins. It is important we keep researching and working towards further understanding and effectively extracting the venom from these animals with as little harm as possible. We have only scratched the surface of all the possible pharmaceutical drugs that can be acquired and created from animal toxins.
Bibliography
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Coulter-Parkhill, A., McClean, S., Gault, V. A., & Irwin, N. (2021, March 27). Therapeutic Potential of Peptides Derived from Animal Venoms: Current Views and Emerging Drugs for Diabetes.
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