Instead of a sleeping pill or a mood enhancer, a nose full of jasmine from Gardenia jasminoides could also help: in collaboration with Dr. Olga Sergeeva and Prof. Helmut Hass from the Heinrich Heine University in Düsseldorf, researchers from Bochum led by Prof. Dr. Dr. Dr. Hanns Hatt have discovered that the two fragrances Vertacetal-coeur (VC) and the chemical variation (PI24513) have the same molecular mechanism of action and are as strong as the commonly prescribed barbiturates or propofol. They soothe, relieve anxiety and promote sleep. The researchers have now been granted a patent for their discovery. They report in the current issue of the Journal of Biological Chemistry (online).
Every fifth German takes a sedative once a year
Sedatives, sleeping pills and relaxants are the most frequently prescribed psychotropic drugs. The difference between calming and hypnotic effect depends solely on the dosage. The classes of substances that exert a calming effect include alcohol, barbiturates, opiates, and since the 1950s, the benzodiazepines, which are now among the world's most widely prescribed drugs. In the course of a year, about 20 percent of all Germans take such drugs or are treated with them for anaesthetic purposes. However, benzodiazepines are not only potentially addictive, but can also cause serious side effects, e.g. depression, dizziness, hypotension, muscle weakness and impaired coordination.
Drugs enhance the effect of the neurotransmitter GABA
Benzodiazepines, barbiturates and anaesthetics such as propofol act via specific adhesion sites on receptors that lie at contact points of nerve cells (synapses) in the brain and increase the effect of the inhibiting endogenous neurotransmitter GABA (gamma-aminobutyric acid). In order to act like GABA itself, the medication would have to be highly dosed, but even lower doses are sufficient to increase the effect of endogenous GABA two to threefold.
Fragrances instead of tablets
The RUB researchers have now performed a large screening study in which they tested hundreds of fragrances to determine their effect on GABA receptors in humans and mice. The two fragrances vertacetal-coeur (VC) and the chemical variation (PI24513) were the strongest: they were able to increase the GABA effect by more than five times and thus act as strongly as the known drugs. The "cross check" with genetically modified GABA receptors in transgenic mice which no longer responded to propofol confirmed that the mechanism of action is the same: the altered receptor also no longer responded to the fragrances.
Fragrances for sleep disorders and stress
Behavioural tests with mice in Prof. Lübbert’s laboratory in the Department of Animal Physiology at the RUB then eliminated the last doubts concerning the qualities of fragrance as a sedative. Injected or inhaled, the fragrances generated a calming effect: in a Plexiglas cage whose air contained a high concentration of the fragrance, the mice ceased all activity and sat quietly in the corner. Via the air breathed in, the scent molecules go from the lungs into the blood and then transmitted from there to the brain. Electrophysiological measurements of neurons in the brain areas responsible for the sleep-wake cycle showed that the GABA-effect on those nerve cells active in sleep was enhanced by the fragrances. “We have discovered a new class of GABA receptor modulator which can be administered parentally and through the respiratory air,” says Prof. Hatt. “Applications in sedation, anxiety, excitement and aggression relieving treatment and sleep induction therapy are all imaginable. The results can also be seen as evidence of a scientific basis for aromatherapy.” By changing the chemical structure of the scent molecules, the researchers hope to achieve even stronger effects.
Olga A. Sergeeva, Olaf Kletke, Andrea Kragler, Anja Poppek, Wiebke Fleischer, Stephan Roger Schubring, Boris Goerg, Helmut L. Haas, Xin-Ran Zhu, Hermann Luebbert, Guenter Gisselmann, and Hanns Hatt: Fragrant dioxane derivatives identify β1 subunit-containing GABA(A) receptors. J. Biol. Chem. jbc.M110.103309 First Published on May 28, 2010, doi:10.1074/jbc.M110.103309
More informationProf. Dr. Dr. Dr. Hanns Hatt, Department of Cell Physiology, Faculty of Biology and Biotechnology at the Ruhr-Universität, 44780 Bochum, Tel. 0234/32-24586
Hanns.Hatt@rub.deDr. Guenter Gisselmann, Department of Cell Physiology, Faculty of Biology and Biotechnology at the Ruhr-Universität, 44780 Bochum, Tel. 0234/32-24586
Editor: Meike Drießen
Dr. Josef König | idw
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