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Show TT 7 V v .v . THE GREEN SHEET Thursday, November 21, s 00 9 l 3 V.J 33 :'. I tf I ta I ... Anti-epileps- suffer seizures which cannot medication. Dr. Swinyard with be yet prevented directs antiepileptic drug development at the college where over 9,000 chemical substances are 250,000 Americans Contest Determines Mascot tested. y Drugs Being Developed At UofU SALT LAKE. Enemas, ammonia water, a plaster of pigeon dung, sneezing powders and drops of human skull extract were considered among the best treatments for epilepsy in 1685. They also were ineffective: King Charles II died after treatment. Although antiepileptic drugs are more sophisticated in 1985, they are still inadequate therapy for half of the 2.5 million Americans who suffer from the disorder. Their only hope is the development of new drugs, many of which initially are tested at the University of Utah. For the past 10 years, Ewart A. Swinyard, Ph.D., professor emeritus of pharmacology, has directed the Antiepileptic Drug Development Laboratory in the University's College of Pharmacy. Over 9,000 chemical substances from academic centers and pharmaceutical industries worldwide have been tested at the laboratory, the only one of its kind. It's supported by the Epilepsy Branch, National Institutes of Neurological and Communicative Disorders! and'' Stroke, a part of the National Institutes of Health ( NIH ) . "A 1970 NIH study found that 50 percent of the people with epilepsy could not be controlled with available drugs," explained Dr. Swinyard. "At that time, no pharmaceutical firm had an active drug development program. So the NIH decided to start a program of its own." Utah was selected as the site for the trials in rodents. Epilepsy is a disorder of the brain, characterized by excessive electrical discharges. Every month, 250,000 Americans have a seizure, according to Dr. Swinyard. Other people depend upon medication to prevent seizures but often must withstand side effects. When the NIH solicits experimental compounds from around the world, they are sent to the University's laboratory, where they undergo as many as seven phases of testing, depending upon results of the initial screening. Mice are used in the first five phases of testing and rats in the last two. Animal models are essential in studying new compounds, explained Dr. Swinyard. "You can call up chemical structures on a computer, but you can't stimulate a living pre-clinic- response to organism'simbalance. neurological "We still not do a completely understand how seizures are brought about," he said. "It's entire-I- y possible that the neurological imbalance could be restored with some neurochemical agent that is not an anticonvulsant. "Once we know if that is the case, we may, in the distant future, be able to test antiepileptic drugs with computers. But we still will use animal models, which have proven reliable and predictable, to validate any new models." In Phase I of the testing, anticon vulsant identification, chemical entities are tested to determine which prevent seizures. The compounds are injected into the periotoneal cavity of mice, and seizures are induced with 0.2 seconds of from 10 to 12 years to develop a new drug, said Dr. Swinyard. Winners of the Sunrise elementary mascot contest were announced at a special "I Care" assembly Friday. Two grand winners were chosen. The name of the new mascot, "Sunny Riser," was submitted by Jamie Blanda. Wesley Matthews designed the costume for the mascot, a colorful sun of yellow and red with red cap and boots. PTA volunteer Mary Ann Duckworth transferred the idea for SANDY. Researchers evaluate the compound's neurotoxicity using the rotorod ataxia test in Phase 2, anticonvulsant quantification. Mice are placed on a slowly revolving rod. Normally, they can maintain their balance; if they experience any neurotoxicity, they slip off the rod within minutes. Researchers also determine the chemical's time of peak effect. Only compounds that show anticonvulsant activity proceed to Phase 3, a neurotoxicity profile. Mice are given different dosages of the chemical entities and observed for up to 24 hours. Researchers look for signs and symptoms of toxicity, including changes in skin color, motor activity and respiration. Phase 4, quantification, is similar to Phase 2, but the mice are given the compounds orally rather than This allows researchers to study rates of absorption, which is important, because most antiepileptic drugs are administered orally. If absorption is adequate, compounds enter Phase 5, antiepileptic drug differentiation. Their ability to prevent various types of seizures and to bond to known drug receptors is compared to that of clinically-effectiv- e drugs, enabling 1 M 90-d- 5 PC. 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They included Michael Gagon, Melissa Thayne, Kellianne Duckworth, McKendrick Babble and Jamie Triptoe. Names of all those who entered were read at the assembly, Janet Gustavson, PTA publicity, said. All students who entered the contest received a certificate and a sucker m in- vestigators to understand the new compounds' mechanisms. In Phase 6, anticonvulsant quantification, the chemical entities are administered orally to rats, primarily as a control to verify results in another rodent species. Rats also are used in Phase 7, a five-da- y chronic study to see if animals develop tolerance to repeated administration. Since antiepileptic drugs must be taken daily, this study is critical. Researchers also watch for the compound's effects on different organs such as the liver and chemical's interaction with other drugs people might take. Of the more than 9,000 compounds submitted to the laboratory, only about 100 have gone through, or are in the process of going through, all seven phases of testing, according to Dr. Swinyard. Of these, 17 have been submitted by the NIH to a commercial laboratory in the East for a toxicity study in rats and dogs. Only after successful completion of this study will a compound undergo clinical trials in human volunteers Ten of these novel compounds arc in the early stages of clinical investigation, two of which are being tested at the University's Drug Resei ach Center, located in University Hospital. Researchers expect that this long-tereffort soon will result in the availability of several new antiepileptic drugs. It usually takes ft struck" by th appearance of Sun E. Riser, the school's new mascot. The costume was made by Mrs. Mary Ann Duckworth. BLINDING . . . Sunris lemntary students Nathan and Garrett Holbrook (kneeling), Brent Noble and Kellie and Ryan Duckworth seem "sun DEVELOPING ANTIEPILEPTIC DRUGS Dr. Edward A. Swinyard, professor emeritus of pharmacology at the UofU College of Pharmacy, tests for neurotoxicity in a mouse that has been injected with ontieplleptic compound. Every month some 1985 485-280- 4 . R UQ U OPEN 10-- 6 Mon.-Sa- t. SUNDAY 12-- 5 p.m. |