In any field, breaking new ground in order to create something entirely new is difficult when past achievements (and past processes) stare you in the face. However, scientists are declaring a new dawn within the field of anesthesia. For the first time since the 1970s, University of Pennsylvania researchers have developed a new technique for identifying potential compounds, which may lead to the next generation of anesthetic drugs.

"The anesthetics identified by this approach require further development before they can be considered for use in the OR," said Dr. Roderic G. Eckenhoff, lead author of the study and professor, Perelman School of Medicine, University of Pennsylvania. "However, the study results show that novel anesthetics do exist."

Eckenhoff and his colleagues began their search for new drugs with an observation: In recent years, most new drugs have come about as mere modifications of existing chemical structures. To discover truly novel drugs, the researchers hypothesized, we most likely need to find an entirely new approach.

With this self-challenge in mind, the researchers began their search by first deciding to use a high-throughput screening process to identify potential compounds. This process allowed them to test over 350,000 compounds and analyze their interactive capabilities with a surrogate anesthetic binding protein target, apoferritin. Among the hundreds of thousands of candidates, the researchers found a subset of 2,600 with the right interactive and structural criteria to be tested for anesthetic activity, first on tadpoles and then on mice. After performing these tests, the researchers “identified four compounds with high potency and low toxicity in tadpoles” yet only “two were found to be effective novel anesthetics in mice,” wrote the authors in their study.

From Many, Two

"While physician anesthesiologists have improved the safety of anesthesia over the years, there are still many risks associated with general anesthesia,” Eckenhoff stated in a press release. “And yet, no new anesthetics have been developed for more than 40 years.”

The war chest of anesthesiology drugs includes inhalational anesthetics and intravenous anesthetics, which are commonly delivered together. Generally, the injection induces a state of unconsciousness and gas maintains it. While the effects of anesthesia drugs are crystal clear, surprisingly little is known about how these chemical agents work.

"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," Eckenhoff said.

Source: McKinstry-Wu AR, Weiming B, Ganesha R, et al. Discovery of a Novel General Anesthetic Chemotype Using High-throughput Screening. Anesthesiology. 2015.