Hamburg  - A new anti-anxiety medication will be able to calm patients' jangled nerves without such annoying side-effects as drowsiness, drug intolerance and withdrawal pangs, according to a team of German scientists.

Scientists working under Dr Rainer Rupprecht at the Max Planck Institute of Psychiatry in Munich succeeded in proving, for the first time, that new anxiolytics can be developed using an innovative mechanism based on neurosteroids derived from the hormone progesterone.

This kind of drug displayed significantly fewer side effects, both in the animal tests and in clinical trials, according to the findings published in the journal Science.

They examined the effect of a new class of substances in co-operation with the Department of Psychiatry of the Ludwig Maximilian University in Munich and the Novartis pharmaceutical concern in Basel.

The substance in question, XBD173, had a positive influence on the synthesis of the body's neurosteroids and, as the scientists were able to prove with the help of mouse brain tissue, triggered the attenuation of neuronal communication as a result. XBD173 also displayed an anxiolytic effect on the behavioural level in the animal model without observing any sedating effects that arise, for example, with benzodiazepines.

"I am absolutely delighted that the hypothesis we developed years ago, that anxiolytic effects can be attained by influencing the body's neurosteroids, has been scientifically confirmed today," says Dr Florian Holsboer, one of the researchers.

In order to test the effect of XBD173 in humans for the first time, the doctors designed a clinical trial, in which 70 healthy volunteer subjects were tested. The subjects were injected with the neuropeptide fragment CCK-4, which triggered a short anxiety and panic attack lasting two to five minutes.

When XBD173 was also administered to the subjects, the panic attack could not be triggered in this way. The benzodiazepine Alprazolam also curbed feelings of anxiety.

However, in contrast to XBD173, the participants in the trial reported undesired fatigue on taking the drug and withdrawal symptoms on its discontinuation.

Thus, through the stimulation of neurosteroid synthesis using the translocator protein 18, the researchers discovered a new mechanism for the treatment of anxiety disorders that displays a better side-effect profile than benzodiazepine. In addition, the conditions were defined under which such studies can be carried out on healthy subjects.

"The successful implementation of an experimentally inducible anxiety model in healthy subjects will facilitate the development of innovative anxiolytics in the future, as the testing of active ingredients in their early phase of development does not necessarily have to be carried out on patients," says Rupprecht.

He warns, however, that insights gained on healthy subjects cannot necessarily be transferred to patients on a one-to-one basis.

"They do not replace the necessary acceptance tests on patient groups," he cautions, adding that more research is needed. (dpa)