Researchers are using sophisticated and powerful new tools to develop and evaluate new anesthetic agents with important advantages over current drugs, according to a set of papers in the August issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).
The new techniques open the way to rapid development of better, safer anesthetics with real benefits for patient care, according to an accompanying editorial by Dr Ken B. Johnson of University of Utah, Salt Lake City.
Advanced Techniques Used to Design Better Anesthetics The August A&A reports on the development and initial evaluation of two new anesthesia agents. Separate research groups are using a combination of older and newer techniques -- including molecular-level techniques and computer stimulations -- for "fast, clean, and soft" drug development. Using these advanced techniques enables researchers to achieve "faster" development of anesthetics that are "softer," with more predictable effects and metabolism; and "cleaner," without unwanted side effects.
Researchers at Massachusetts General Hospital, Boston, report on the development of an improved version of etomidate -- a sedative commonly used to induce general anesthesia in patients who are elderly, critically ill, or in unstable condition. Unfortunately, etomidate also causes suppression of adrenocortical function. This can interfere with production of steroid substances that play an important role in immunity and other key functions.
The researchers identified the specific feature of the etomidate molecule -- a "pyrrole ring" -- responsible for blocking adrenocortical function. Armed with this knowledge, they modified the pyrrole ring to created new versions of etomidate. They report initial pharmacological studies of a new "MOC-carboetomidate" that combines the potent sedative activity with rapid metabolism and clearance from the brain. The new drug promotes hemodynamic stability, without suppressing adrenocortical function.
A group of researchers from PAION UK, Ltd, and Johns Hopkins University School of Medicine report on the development a new benzodiazepine-type sedative drug called remimazolam. Again, molecular-level techniques were used to create a new benzodiazepine drug with more favorable properties: "fast onset, a short, predictable duration of sedative action, and a more rapid recovery profile than currently available drugs."
The researchers report the use of computerized models and simulation techniques to explore the basic properties of the remimazolam. The results suggested very rapid sedation, reaching peak effect within three minutes, which should allow more accurate tailoring of the final dose.
The new techniques may facilitate the evaluation of remimazolam from initial human studies to final clinical trials. Dr Johnson also notes that some of the simulation techniques used in the studies provide useful and detailed information for anesthesiologists to use in comparing the effects of different anesthetics.
The new reports provide a timely illustration of the way anesthesiology researchers are using advanced techniques to develop and introduce new agents that will help to make anesthesia more effective and safer for patients. Dr Johnson concludes, "Through their efforts, remimazolam and the MOC etomidate analogs will likely bring interesting advances to our specialty in the coming years!"
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