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Biological Chemistry

Tadpole Tests Confirm Light-Activated Anesthetic Is Reversible

Small molecule enables reversible command of a neurotransmitter’s activity

by Carmen Drahl
September 24, 2012 | APPEARED IN VOLUME 90, ISSUE 39

Credit: Angew. Chem. Int. Ed.
Shining blue-violet light awakens AP2-anesthetized tadpoles, but not propofol-anesthetized ones.
Credit: Angew. Chem. Int. Ed.
Shining blue-violet light awakens AP2-anesthetized tadpoles, but not propofol-anesthetized ones.
Credit: Adapted from Angew. Chem. Int. Ed.
Watch the switchable anesthetic AP2 turn off with a flash of blue-violet light, awakening anesthetized tadpoles, and listen to why an expert in anesthetic probes thinks this advance could help researchers figure out how general anesthesia works.

With a switchable version of a popular anesthetic, researchers can now use light to control another important neurotransmitter receptor, the GABAA receptor (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201205475). Scientists have already controlled animals’ heartbeat, pain, and visual response with light-activated blockers of ion channels in the nervous system. To command GABAA, a chloride channel, Dirk Trauner of the University of Munich, Erwin Sigel of Switzerland’s University of Bern, and coworkers made azobenzene derivatives of the anesthetic propofol. GABAA plays a major role in propofol’s activity, though the molecule’s mode of action is not entirely clear. In the dark, the azo-propofols are in the trans form and increase GABAA’s chloride current. Upon exposure to blue-violet light, they convert to the cis form, reversing the effect. The team’s best compound so far, AP2, reverts to the trans form on its own, because its amino group makes the cis form unstable. Tadpoles exposed to trans-AP2 are anesthetized, but shining blue-violet light rapidly wakes them. Trauner isn’t sure how applicable AP2 will be in clinical anesthesia, but his team plans to study its activity in retinas, because GABAA also is involved in the biology of vision.



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