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Understanding alcohol's effects may improve drug design (6/21/95)Would you take a mind-altering drug even though no one knows how it works? You probably already have and a physician may even have prescribed it. According to neuropharmacologist Maharaj K. Ticku, PhD, many drugs are used by the public and even prescribed by physicians before their exact mechanism of action is understood. Although millions use the "over-the-counter" drug ethanol, commonly known as alcohol, for example, scientists still don't know exactly how it affects the brain. Researchers at The University of Texas Health Science Center at San Antonio led by Dr. Ticku are studying the brain's reaction to ethanol with an eye to applying that understanding to other psychoactive drugs. Supported by federal funding for these studies since the 1980s, Dr. Ticku is trying to define the molecular mechanisms that occur in the brain when it is exposed to alcohol. "We hope to explain, for example, a person's tolerance or adaptation to alcohol and what happens as a result of various drinking patterns such as those of the nighttime drinker, whose brain is daily undergoing withdrawal, versus the person who drinks all the time," Dr. Ticku says. His most recent grant is a five-year, $915,108 award from the National Institute of Alcohol Abuse and Alcoholism to study "Chronic Intermittant Ethanol and GABA and NMDA Receptors." GABA is a brain chemical that inhibits nerve activity and NMDA is another type of brain chemical, that stimulates nerve activity in the brain and is involved in memory and learning. "We know that alcohol increases GABA mediated inhibition and suppresses NMDA receptors," he says. "That leads us to believe that maybe the short term memory loss experienced by some people who drink is caused by NMDA being suppressed, while the relaxation they experience may be caused by another chemical reaction - the GABA effect. One of our ultimate goals is to sort out and define the mechanisms of action of these chemicals so that we can better target and tailor drug therapy that affects the brain to achieve specific effects and avoid unwanted side effects." Alcohol is not the only psychoactive chemical that has made it to the marketplace before scientists could explain how it works. "A few years after the tranquilizer Valium was approved for prescription in 1963 an estimated 50 million prescriptions for Valium-like drugs were written and Americans were estimated to have taken 8,000 tons of the medication by 1977," Dr. Ticku recalls. "Scientists didn't know exactly how it was doing what it was doing in the brain until 1978." Dr. Ticku and colleagues have used test animals in the past, but currently are working with cells in the laboratory. "We are using mammalian cortical neurons in culture," he says. "We know that NMDA is defined by five different genes and that GABA is defined by 16 different genes. We are using a multifaceted approach including looking at these genes, at chemical receptors in the brain, at functional ability, and at proteins in the brain." he says. Dr. Ticku was one of the first scientists to hypothesize more than 10 years ago that alcohol has selective effects on proteins in the brain. This has since been shown. "Once we are able to define what is happening in the brain when a chemical such as alcohol is introduced, we may be able to use this knowledge to design drugs to affect specific receptors formed by specific genes," Dr. Ticku says. "This could help provide better drugs for all sorts of uses, ranging from anesthesia to control of epilepsy, anxiety and premenstrual problems." Contact: Mike Lawrence (210) 567-2570
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