By WILLIAM McCALL
October 20, 1999
Valium and similar tranquilizers used to treat anxiety and insomnia could be reformulated to reduce such side effects as clumsiness and memory loss, a study suggests.
Changing the drugs might also prevent them from intensifying the effects of alcohol, according to the study, reported in Thursday's issue of the journal Nature.
The study, involving genetically engineered mice, was conducted by researchers at the University of Zurich, the Swiss Institute of Technology and Swiss pharmaceutical giant F. Hoffmann-LaRoche Ltd., which makes Valium.
``I think the results are quite exciting because there has been a lot of talk over the years about whether the therapeutic effects of tranquilizers can be isolated,'' said Dr. Patricia Kroboth at the University of Pittsburgh School of Pharmacy.
Human and animal brains are wired with receptors for gamma-aminobutyric acid, or GABA, a molecule that regulates mental states such as anxiety. Valium, or diazepam, is part of a family of drugs called benzodiazepines - including Halcyon and Librium - that ease anxiety by making the GABA receptors act more efficiently.
The problem is that GABA receptors are found throughout the brain, so Valium affects other circuits, such as those that control attention and balance.
The Swiss researchers created genetically altered mice in which one kind of GABA receptor was insensitive to benzodiazepines. That blocked some of the side effects of Valium.
Normal mice given Valium became sluggish, relaxed and showed poor memory, failing to remember how to avoid an electric shock. The gene-altered mice given the same dose remained active and avoided the shock.
Researchers believe they can remake the tranquilizer, instead of the receptor, to work only on the specific GABA receptors in the brain that control anxiety.
A small change in the chemical formula of Valium could allow people to take it without worrying about loss of memory or coordination, or possibly even addiction, said Hanns Moehler of the University of Zurich.
GABA receptors are nearly identical in humans and animals and work about the same way, Moehler said. But experts said any new versions of Valium and other tranquilizers are years off.
