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Show The Daily Uuh Chronicle, Monday, September 30, 1985 Page Thirteen Ressamchoirs test mice ffoir co ire of ssozuires 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 they are still inadequate therapy for half of the 2.5 million Americans who suffer from the 1985, disorder. Their only hope is the development of new drugs, many of which initially arc tested at the University of Utah. For the past 10 years, Ewart A. Swinyard, professor emeritus of pharmacology, has directed the Antiepileptic Drug Development Laboratory in the College of Pharmacy. Over 9,000 Us 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 Institute of prevent seizures but often must withstand side effects. When the NIH solicits experimental compounds from around the world, they are sent to the U.'s laboratory where they undergo as many as seven phases of testing, depending upon results of the initial screening. "We still do not completely understand how seizures are brought about," he said. "It's entirely 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 models." In Phase I of the testing, anticonvulsant identification, chemical entities are tested to determine which prevent seizures. The compounds are injected into the peritoneal cavity of mice, and seizures are induced with 0.2 seconds of electroshock. Health (NIH.) "A 1970 NIH study found that 50 percent of the people with epilepsy could not be controlled with available drugs," explained Swinyard. "At that time, no pharmaceutical firm had an active antiepileptic 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. a Epilepsy is disorder of the brain, also determine the chemical's time of peak effect. Only compounds that show anticonvulsant activity proceed to Phase 3, a Americans have a seizure, Swinyard said. Other people depend upon medication to different dosages of the chemical entities and observed for up to 24 hours. Researchers look for signs and symptoms pre-clinic- al characterized by excessive electrical discharges. Every month, 250,000 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 withing minutes. Researchers Ik : i . V"7o ff A Ewart A. Swinyard, professor emeritus of pharmacology at the University of Utah College of Pharmacy, tests for neurotoxicity in a mouse that has been injected with an antiepileptic. 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 law 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-effectidrugs enabling investigators to ve compounds orally rather than intra peritoneally. This allows researchers to study rates of absorption, which is 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. important because most antiepileptic drugs are administered orally. If absorption is adequate, compounds JJcbc Pcrt-TIcn- o neurotoxicity profile. Mice are given asm 7 V' s On Carapus $4.75 plus weekly bonuses. 5:30-9:3- 0 p.m. Sunday-Thursda- y; Pay: Hours: minimum three nights a week. Work begins October 7 for approximately 6 weeks. (is Description: Telephone solicitation of university alumni and friends. Qualifications: Interpersonal and skills command of the English language required. d Must be and willing to take instructions. Telephone experience helpful. well-organiz- detail-oriente- ed, Contact: 1. He loses arguments gracefully 8. He opens doors fop me and follows other rules of chivalry without flinching. 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