2004-02-13

Valerian, a herb native to Europe and used for more than 2,000 years to treat anxiety and insomnia, until recently was thought to work by increasing the activity of GABA (gamma amino butyric acid), a neurotransmitters in the brain that dampens down the transmission of nerve impulses.

This is the target of the benzodiazepine class of anxiety drugs, which are a mainstay of treatment for acute anxiety disorders.

However, new research at the University of Bonn in Germany has identified a previously unidentified compound that seems to exert an anxiolytic effect by interacting with adenosine A1 receptors.

It is already known that stimulating the A1 receptor can induce sleep, but adenosine itself is too short-lived in the body to have such an effect. Conversely, caffeine blocks these receptors and has the opposite effect, causing wakefulness.

After coming across a study showing that valerian interacts with adenosine receptors, the researchers, headed by Christa Müller, professor of pharmaceutical chemistry at Bonn, tested a number of extracts of valerian to try to identify the compound having this effect.

Lignan compound

In collaboration with the University of Marburg, the Bonn team narrowed down the search to a member of the lignan group. This compound was found to bind to both animal and human A1 receptors in the same way as adenosine.

Stable adenosine A1 agonists have been developed, but their use in anxiety is problematic because A1 receptors also occur in heart muscle, raising the risks of life-threatening side effects such as myocardial paralysis.

"Our lignan, in contrast, is a partial agonist, i.e. it only kicks in when there is a high density of receptors in the brain," said Prof Müller.

As yet it is still completely unclear how the lignan is recognised by the A1 receptor, as it has hardly any structural similarity to adenosine. The Bonn researchers now intend to attempt to find the parts of the molecule essential for this activity in the hope of finding a candidate suitable for clinical development in humans.

Meanwhile, studies comparing the effects of valerian extracts and caffeine on sleep, conducted by Swiss pharmaceutical company Zeller, lend weight to evidence that valerian does indeed act via the A1 receptor.

The company's scientists looked at the effects of caffeine and valerian extracts on the brain waves of just under 50 test subjects. After caffeine was ingested the alpha waves signalling relaxation levelled out; by contrast, the beta waves, signs of nervousness, became more marked. When valerian extract was administered, this effect was neutralised.