>Delivered-To: chronicpain@apollo.dns-solutions.net >Date: 14 Feb 2000 23:30:58 -0000 >From: jim@goedhart.com >To: chronicpain@list.goedhart.com >Subject: [chronicpain] TINY FROG OFFERS MAJOR NEW PAINKILLER >Sender: owner-chronicpain@list.goedhart.com >Reply-To: chronicpain@list.goedhart.com > >TINY FROG OFFERS MAJOR NEW PAINKILLER, DRUG RESEARCH FINDS > >QUITO, Ecuador -- Epibpedobates tricolor seems a big name for something so >small. > >Little longer than a fingernail, the tiny frog can easily hide in the heart >of a flowering plant, a bright jewel of red and green with shining black >eyes. > >The brilliant color is a warning. The frog's skin secretes a deadly poison, >which Ecuador's rain forest dwellers have long used to coat blowgun darts >for hunting. When the poison enters the bloodstream of a monkey or sloth, >the animal quickly dies. > >Soon, however, Epibpedobates tricolor also may become a boon for mankind. > >Abbott Laboratories of North Chicago has just completed initial human >trials in Europe of a painkilling drug based on a derivative of the frog's >poison. While the results have not yet been made public and the company is >hesitant to talk about ABT-594, as the chemical is known, scientists say >the drug is 200 times as powerful as morphine, lacks morphine's addictive >problems, and might one day take that drug's place as the world's leading >treatment for intense and chronic pain. > >"Abbott, I think, was very lucky to be able to separate the toxicity from >the desired analgesic effect," said John Daley, a scientist at the National >Institutes of Health who initially identified the chemical structure of the >frog poison. > >With many drugs derived from natural substances, such as digitalis used in >the treatment of heart problems, "nobody's been able to get rid of the >toxicity. That's usually the problem," he said. > >ABT-594, however, has passed its initial human trials, which determine >whether the drug produces problem side effects in healthy users. Phase II >trials, in which the drug will be tested on pain sufferers, are being >scheduled, said Melissa Brotz, an Abbott spokeswoman. > >"We'll probably try a broad brush on a few different types of pain," she >said. > >Years of research into compounds from rain forest plants, animals and >insects are beginning to pay off for companies such as Abbott, which >synthesized up to 500 variations of the Epibpedobates frog poison before >deciding to go forward with ABT-594. > >Scientists say they expect to see a growing number of drugs coming out of >the world's tropical rain forests. What is more worrying is whether the >rain forest and its animals will still be there to provide their >potentially miraculous compounds in the future. > >The tiny frog that gave birth to Abbott's new painkiller is endemic to >lowland rain forest slopes in southwestern Ecuador, near the town of Loja. >Today, less than 6 percent of the frog's original habitat remains intact. > >When Daley first came to Ecuador in the late 1970s to collect samples of >the frog, he was able to take home more than 750. Within a few years, road >building and human settlement put the frog on Ecuador's threatened species >list and further collecting was outlawed. > >"Human competition is their worst problem," said Maria Elena Baragan, >director of Quito's vivarium, which displays a collection of the tiny >poison dart frogs. > >Today, the frog has managed somewhat of a comeback by adapting to life in >Ecuador's coastal banana plantations, where it is commonly found. The >problem is that in its altered habitat or in captivity the frog no longer >produces its poison. > >Scientists have not yet determined what it is about the frog's forest >habitat that allows it to produce the vital chemical. "There just are no >studies," Baragan says. But work on some of the other 100 or so species of >poison dart frogs suggests it is probably some ant, millipede or beetle in >the frog's diet. > >"The frog without its intact surroundings is useless," said Roderick Mast, >a vice president and frog expert at Washington-based Conservation >International. "It's a wonderful conservation flagship species. You have to >conserve its entire habitat to conserve it." > >Whether the frog and its habitats will be protected, however, remains in >question, in part because Abbott's new drug, a variation of the natural >frog poison, can be synthesized in the laboratory without the frog. > >That ability is a blessing for native frog populations that might otherwise >be decimated by collecting for medical purposes and a curse in that their >protection is no longer key to development of the drug. > >Countries such as Ecuador, which are only now working on laws to claim >intellectual property rights on the genetic variety in their forests, >generally get no share in the profits of new drugs produced from their >plants or animals. > >Other countries have passed laws that patent the genetic material but not >derivatives of it, the case with ABT-594. > >That has left many South American countries with little money for or direct >interest in promoting conservation of their rain forest species. > >Mast calls that shortsighted and says part of the answer is for countries >such as Ecuador, Colombia, Brazil and Peru to begin strengthening their >drug industries to take advantage of their resources. > >"Our basic understanding of biodiversity is pathetic," he said. "We barely >know what species are out there let alone the alkaloids they have in their >skin or what they might be good for. > >"How many chemicals are out there? We have no idea. What we do know is that >we're only scratching the surface." > >When the chemical structure of the Epibpedobates frog poison was determined >in 1990, Daley found that the chemical worked as a powerful painkiller but >not through the same opioid receptors targeted by morphine. > >Abbott's non-toxic derivative focuses instead on nicotine receptors, >raising the possibility that other kinds of addiction might be a problem. >So far, however, the company has reported no addiction problems and early >testing in rats showed animals taken off the painkiller suffered no lack of >appetite, a normal withdrawal sign. > >The drug also appears to make users alert, rather than sedating them, as is >the case with morphine. > >"Abbott got the jump on everyone else on this because they have been >working on nicotine derivatives forever," Mast said. "They weren't >particularly looking for painkillers but as a good chemical company they're >always on the lookout. This popped up as something with potential." > >If the drug eventually wins U.S. approval from the Food and Drug >Administration, a process Abbott says is still years away, it could >potentially snare a major share of what is a $40 billion a year worldwide >industry in treating long-term or severe pain not affected by aspirin or >other basic painkillers. > >In the U.S., the company estimates 30 million to 40 million people suffer >pain that might be treated by ABT-594. > >Mast calls the promising new drug reason enough to step up conservation of >rain forests, where he and others believe many other new wonder drugs lurk. >