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Researchers Make Breakthrough in Search for New Anesthetics

Novel approach may lead to next generation of better, safer anesthetic agents

For the first time since the 1970s, researchers are on the verge of developing a new class of anesthetics, according to a study published in the February issue of Anesthesiology.

“While physician anesthesiologists have improved the safety of anesthesia over the years, there are still many risks associated with general anesthesia. And yet no new anesthetics have been developed for more than 40 years,” said lead author Roderic G. Eckenhoff, MD, Professor of Anesthesiology and Critical Care at the Perelman School of Medicine at the University of Pennsylvania. “We are only beginning to understand the actual mechanisms that allow general anesthetics to achieve an anesthetized state, and this study is a breakthrough into that world.”

According to Eckenhoff, the search for new anesthetics has historically been a mixture of empiricism and serendipity. Researchers routinely modify existing anesthetic drugs, rather than develop an entirely new class of anesthetics.

Eckenhoff and his team sought to prove that a new approach could reveal completely new anesthetic structures. Their approach, often used in drug development for therapeutics, but never before with anesthetics, identified two new anesthetic compounds that have the potential to be used in humans.

In collaboration with the Chemical Genomics Center of the National Center for Advancing Translational Sciences (NCATS), the researchers used a screening process that allowed them to test more than 350,000 compounds for their potential to serve as anesthetic agents. The compounds were evaluated for their ability to bind a surrogate anesthetic binding protein target, apoferritin.

Among the 350,000 compounds, the researchers found 2,600 that showed strong interactions with apoferritin. A subset of these compounds was chosen, based on structural criteria, to be tested for anesthetic activity in animals. The researchers concluded that two compounds could potentially serve as anesthetics for humans.

“The anesthetics identified by this approach require further development before they can be considered for use in the OR,” Eckenhoff said. “However, the study results show that novel anesthetics do exist, and that we need not restrict ourselves to small modifications of existing drugs.”

Source: ASA; January 20, 2015.

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