Venom-Based Remedies Used For Centuries
October 22, 2018 at 3:43 p.m.
By Max [email protected]
To date there have been seven FDA-approved venom-derived drugs as a result of modern research:
• Exenatide, is made from the saliva of the Gila monster and is used in treating type 2 diabetes.
• Ziconotide is the synthetic equivalent of a peptide found in the venom of a marine snail and used for chronic pain.
• Captopril is derived from the Brazilian pit viper and used to manage high blood pressure.
• Eptifibatide and Tirofiban are anti-platelet drugs derived from rattlesnake or viper venoms used to prevent blood clots.
• Lepirudin and Bivalirudin, thrombin inhibitors, are synthetic derivatives of hirudin, a compound excreted from the medicinal leech.
Purists may argue that some type of venom has been used to treat patients long before any of these products. Snake venom, for example, was used since the 7th century B.C. to prolong life and treat arthritis and gastrointestinal ailments, while tarantulas are and were used in the traditional medicine of indigenous populations of Mexico and Central and South America.
A number of antivenin preparations also are available for treating snakebite, and equine-derived antivenin has been the mainstay of hospital treatment for venomous snakebite for more than 35 years. Antivenin is an antibody preparation derived from horses or sheep injected with non-lethal amounts of snake venom.
For rattlesnake, cottonmouth and copperhead bites, for example, Antivenin (Crotalidae) Polyvalent has been the standard available treatment. Eastern coral snakebites require Antivenin (Micrurus fulvius). A sheep-derived antivenin, CroFab (Crotalidae Polyvalent Immune Fab), has also received approval from the Food and Drug Administration for treating snakebites; it is much less allergenic.
Due to their method of manufacture and their passive use, none of the antivenin products can be considered therapeutic venoms. Captopril, the first of a series of ACE inhibitors, however, can be considered a precursor and is the first example of a venom-based drug. Captopril was developed from structural relationship studies of teprotide, a peptide from Bothrops jararaca venom. Historians may go further back and consider theriac, a remedy developed by Galen in the second century A.D. He developed his concoction containing more than 70 ingredients, including opium, wine and snake meat, to protect against snake bite.
The release of exenatide and ziconotide will likely be the impetus for a host of other therapeutically useful drugs. Venoms are proving to be a remarkable source of novel peptides that have potential applications in human health. A number have already been used for proof of concept studies, some having undergone preclinical or clinical development for treating pain, diabetes, multiple sclerosis and cardiovascular diseases. Toxins that target ion channels and receptors have been isolated from spiders, marine snails, snakes, scorpions and a range of other animals.
Snake venoms have been studied extensively, including their molecular origins, chemical nature and biologic activities. The studies have been aided by new innovations in technologies that map the relationships and actions of the molecular structure of the venom. Researchers now have the ability to uncover evolutionary changes and diversification among specific venomous species that could prove useful in developing new drugs. According to one clinician, knowing more about the evolutionary history of venomous species can help make more targeted decisions about the potential uses of venom compounds in treating disease.
Venoms are made from the same basic molecules as the proteins of the body. They contain short chains of amino acids, called polypeptides, which poison the victim by causing paralysis. Like curare, they act by blocking the action of acetylcholine at the junction between the nerve and muscle. Venomous snakes are known to possess one of the most sophisticated integrated weapons systems in the natural world. Like snakes, Conus venoms also contain a remarkable diversity of pharmacologically active small peptides. Their targets are ion channels and receptors in the neuromuscular system, and a drug derived from the venom could treat autoimmune diseases.
One noteworthy potential drug is chlorotoxin derived from the deathstalker scorpion. It could be the basis for a surgical tumor-imaging technique, and clinical trials to confirm safety and efficacy have already begun. Chlorotoxin actually lights up or stains (paints) malignant tumors and other cancers and could help surgeons resect tumors with the least amount of extraneous damage to surrounding non-cancerous tissues.
With all of the ongoing research there are bound to be a number of surprising new medical developments in store for all of us.
Max Sherman is a medical writer and pharmacist retired from the medical device industry. He has taught college courses on regulatory and compliance issues at Ivy Tech, Grace College and Butler University. Sherman has an unquenchable thirst for knowledge on all levels. Eclectic Science, the title of his column, will touch on famed doctors and scientists, human senses, aging, various diseases, and little-known facts about many species, including their contributions to scientific research. He can be reached by email at [email protected].
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To date there have been seven FDA-approved venom-derived drugs as a result of modern research:
• Exenatide, is made from the saliva of the Gila monster and is used in treating type 2 diabetes.
• Ziconotide is the synthetic equivalent of a peptide found in the venom of a marine snail and used for chronic pain.
• Captopril is derived from the Brazilian pit viper and used to manage high blood pressure.
• Eptifibatide and Tirofiban are anti-platelet drugs derived from rattlesnake or viper venoms used to prevent blood clots.
• Lepirudin and Bivalirudin, thrombin inhibitors, are synthetic derivatives of hirudin, a compound excreted from the medicinal leech.
Purists may argue that some type of venom has been used to treat patients long before any of these products. Snake venom, for example, was used since the 7th century B.C. to prolong life and treat arthritis and gastrointestinal ailments, while tarantulas are and were used in the traditional medicine of indigenous populations of Mexico and Central and South America.
A number of antivenin preparations also are available for treating snakebite, and equine-derived antivenin has been the mainstay of hospital treatment for venomous snakebite for more than 35 years. Antivenin is an antibody preparation derived from horses or sheep injected with non-lethal amounts of snake venom.
For rattlesnake, cottonmouth and copperhead bites, for example, Antivenin (Crotalidae) Polyvalent has been the standard available treatment. Eastern coral snakebites require Antivenin (Micrurus fulvius). A sheep-derived antivenin, CroFab (Crotalidae Polyvalent Immune Fab), has also received approval from the Food and Drug Administration for treating snakebites; it is much less allergenic.
Due to their method of manufacture and their passive use, none of the antivenin products can be considered therapeutic venoms. Captopril, the first of a series of ACE inhibitors, however, can be considered a precursor and is the first example of a venom-based drug. Captopril was developed from structural relationship studies of teprotide, a peptide from Bothrops jararaca venom. Historians may go further back and consider theriac, a remedy developed by Galen in the second century A.D. He developed his concoction containing more than 70 ingredients, including opium, wine and snake meat, to protect against snake bite.
The release of exenatide and ziconotide will likely be the impetus for a host of other therapeutically useful drugs. Venoms are proving to be a remarkable source of novel peptides that have potential applications in human health. A number have already been used for proof of concept studies, some having undergone preclinical or clinical development for treating pain, diabetes, multiple sclerosis and cardiovascular diseases. Toxins that target ion channels and receptors have been isolated from spiders, marine snails, snakes, scorpions and a range of other animals.
Snake venoms have been studied extensively, including their molecular origins, chemical nature and biologic activities. The studies have been aided by new innovations in technologies that map the relationships and actions of the molecular structure of the venom. Researchers now have the ability to uncover evolutionary changes and diversification among specific venomous species that could prove useful in developing new drugs. According to one clinician, knowing more about the evolutionary history of venomous species can help make more targeted decisions about the potential uses of venom compounds in treating disease.
Venoms are made from the same basic molecules as the proteins of the body. They contain short chains of amino acids, called polypeptides, which poison the victim by causing paralysis. Like curare, they act by blocking the action of acetylcholine at the junction between the nerve and muscle. Venomous snakes are known to possess one of the most sophisticated integrated weapons systems in the natural world. Like snakes, Conus venoms also contain a remarkable diversity of pharmacologically active small peptides. Their targets are ion channels and receptors in the neuromuscular system, and a drug derived from the venom could treat autoimmune diseases.
One noteworthy potential drug is chlorotoxin derived from the deathstalker scorpion. It could be the basis for a surgical tumor-imaging technique, and clinical trials to confirm safety and efficacy have already begun. Chlorotoxin actually lights up or stains (paints) malignant tumors and other cancers and could help surgeons resect tumors with the least amount of extraneous damage to surrounding non-cancerous tissues.
With all of the ongoing research there are bound to be a number of surprising new medical developments in store for all of us.
Max Sherman is a medical writer and pharmacist retired from the medical device industry. He has taught college courses on regulatory and compliance issues at Ivy Tech, Grace College and Butler University. Sherman has an unquenchable thirst for knowledge on all levels. Eclectic Science, the title of his column, will touch on famed doctors and scientists, human senses, aging, various diseases, and little-known facts about many species, including their contributions to scientific research. He can be reached by email at [email protected].
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