Azobenzene derivatives of propofol increase GABA-induced currents in the dark form and loose this property upon light exposure and thus function as photochromic potentiators. The coumpound can be employed as a light-dependent general anesthetic in translucent tadpoles.
Dirk Trauner, Professor of Chemical Biology and Genetics at LMU and a member of the Excellence Cluster CIPSM, is a specialist in the art of conferring on "blind" nerve cells the ability to react to light. Working with colleagues based in Switzerland and the US, he has now developed a derivative of propofol that allows the action of the GABA receptor to be regulated by light. "By attaching a molecular switch to propofol, we have obtained a light-sensitive molecule that is a more potent anesthetic than propofol itself, in the dark," Trauner explains.
Sleepless when the sun shines
In this case, light serves to largely inactivate the anesthetic effect of the compound, as the researchers were able to demonstrate in experiments on tadpoles. When exposed to a low concentration of the propofol derivative, the animals were anesthetized, as expected. However, when irradiated with violet light, they promptly revived, but remained active only as long as the light was on. In the dark, they were immobilized once again. The light-dependent effect is completely reversible, as the tadpoles recovered fully upon transfer to their normal aquarium.
The new agent could be used to treat certain forms of blindness, such as retinitis pigmentosa, which leads to loss of vision owing to progressive destruction of photoreceptors. However, neurons deeper in the retina are unaffected, and are accessible to ambient light. "The inner cells also bear GABA receptors on their surfaces, and in principle they could be turned into light-responsive cells with the help of the new compound, which would allow us to bypass the defective photoreceptors," says Trauner. He and his research group are now actively exploring this possibility. (Angewandte Chemie, see below)