Researchers are using molecular techniques and other sophisticated approaches to develop and evaluate new anesthetic agents with important advantages over current drugs.
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
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!"