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Thursday, 5 October, 2000, 18:11 GMT 19:11 UK
New tranquilisers promised
Diazepam
Scientists aim to design new versions of diazepam (Valium)
An "anxious" mouse with a defect in a key part of the brain could lead to a new generation of tranquilisers, say scientists.

By altering the genes of rodents, Swiss researchers have located the specific site that mediates the anti-anxiety effect of drugs such as Valium.

Lab studies revealed that after a dose of medication, normal mice were happy to scamper around in light places.

But "anxious" mice with a genetic mutation preferred to hide in dark corners even after drug treatment.

The mice could help in the discovery of new improved tranquilisers with fewer side effects, say the scientists.

Drugs such as Valium act on the brain by latching on to four sub-types of what are known as GABA A receptors.

The mouse research showed that only one of these sub-types was responsible for the drugs' anti-anxiety effects, said Professor Hans Möller of the University of Zürich and Swiss Federal Institute of Technology, also in Zürich.

Brain pathways

"GABA is like a 'brake system'," he told BBC News Online. "In the presence of benzodiazepine drugs like Valium, the brakes operate more efficiently.

Mouse
'Anxious' mouse follows other gene-altered rodents like this 'super-intelligent' mouse
"Among all those GABA A receptors - brakes in the brain - you need only one receptor sub-type to induce the anti-anxiety effect."

About 25% of people develop an anxiety disorder at some time in their lives. These include phobias, panic attacks and post-traumatic stress disorders.

While tranquilisers can help reduce excessive anxiety, the drugs may also have unwanted side-effects, such as sleepiness, forgetfulness or movement disorders.

The side-effects strike because Valium-type medications latch on to all four sub-types of GABA A receptors.

Drug discovery

By altering the different brain receptor sub-types in lab mice, the scientists have found the particular sub-type responsible for the anti-anxiety effects of tranquilisers.

If scientists can now develop compounds that target this one sub-type alone, they should be able to develop a range of new treatments with far fewer side effects.

"The discovery helps to develop a new type of anti-anxiety treatment which is much more selective than the presently-used benzodiazepine drugs and has dramatically reduced side effects," said Professor Möller.

"The treatment of patients with generalised anxiety disorders, panic attacks or even anxious depression will enter into a new era," he added.

The mouse research is published in the latest edition of the journal Science.

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24 Aug 99 | Sci/Tech
'Scared mouse' joins medical models
14 Jun 00 | Health
'Gene for panic attacks'
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