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New aromatherapy fragrances with Valium-like effect

Posted Aug 14 2010 12:00am - Instead of a sleeping pill or a tranquilizer, a nose full of a fragrance from Gardenia jasminoides could help, according to researchers writing in the Journal of Biological Chemistry.

In collaboration with Dr. Olga Sergeeva and Professor Helmut Hass from the Heinrich Heine University in Düsseldorf, researchers from Ruhr-Universität-Bochum led by Professor Hanns Hatt have discovered that the two fragrances vertacetal-coeur (VC) and a chemical variation (PI24513) have the same molecular mechanism of action and are as strong as the commonly prescribed barbiturates or propofol. In the study, the fragrances were shown to soothe, relieve anxiety and promote sleep. The researchers have now been granted a patent for their discovery.

Oral drugs that enhance the effect of the neurotransmitter GABA

Benzodiazepines (e.g. Valium, or diazepam), barbiturates and anesthetics 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 naturally occurring neurotransmitter GABA (gamma-aminobutyric acid). Apparently even lower doses of such agents have been sufficient to increase the effect of endogenous GABA two to threefold.

Fragrances instead of pills

The researchers performed a screening study in which they tested hundreds of fragrances to determine their effect on GABA receptors in humans and mice. Two fragrances - vertacetal-coeur (VC) and a 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. A “cross check” with genetically-modified GABA receptors in transgenic mice which were modified to no longer respond to propofol confirmed that the mechanism of action is the same for the fragrance and the propofol: the altered receptor no longer responded to the fragrances or the known drugs.

The authors refer to these 2 fragrant dioxane derivatives (FDD) as a “new structural class of GABA-A-R positive modulators with unique β1-subunit selectivity.”

Fragrances for sleep disorders and stress

Behavioral tests with mice in Lübbert’s laboratory then eliminated the last doubts concerning the possible use of the fragrance as a sedative. Injected or inhaled, the fragrances generated a calming effect. When placed in a plastic cage with a high concentration of the fragrance, the mice ceased all activity and sat quietly in the corner. Electrophysiological measurements of neurons in the brain areas responsible for the sleep-wake cycle showed that the GABA-effect on those nerve cells was enhanced by the fragrances.

“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,”  Hatt said. By changing the chemical structure of the scent molecules, the researchers hope to achieve even stronger effects.

The abstract of this fragrance study is available online free here:

Reference: Fragrant dioxane derivatives identify β1 subunit-containing GABA-A receptors. O. A. Sergeeva, et al. Journal of Biological Chemistry, 2010; DOI: 10.1074/jbc.M110.103309

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