In celebration of the 175th anniversary of the birth of anesthesiology, three Mass General pioneers in anesthesia business and research share how they got where they are today, why clinical representation is critical in innovation and the lessons they have learned today.
Departments, Centers, & Programs:
Anesthesia, Critical Care and Pain Medicine
55 Fruit Street
Boston, MA 02114-2696
- MD, University of Virginia School of Medicine
- Residency, Massachusetts General Hospital
American Board Certifications
- Anesthesiology, American Board of Anesthesiology
Accepted Insurance Plans
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- Defining the molecular mechanisms of general anesthetic actionon relevant protein targets: GABAA receptors, NMDA receptors, Serotonin receptors, 11beta-hydroxylase
- Rationally designing new anesthetic etomidate analogues
- Studying the pharmacology of our new drugs in receptor, cellular, and rodent models
Description of ResearchThe main goal of my research lab is to gain a better understanding of how and where general anesthetics act at the molecular and receptor levels in order to build up a pharmacological and mechanistic basis for rationally designing new anesthetic agents. To achieve this goal, we use medicinal chemical, biophysical, electrophysiological, and computational approaches. Much of our current effort focuses on etomidate, an intravenous anesthetic that provides superior hemodynamic stability, but is slowly metabolized and potently inhibits 11beta-hydroxylase. This leads to profound and persistent adrenocortical suppression that is potentially deadly, particularly in the critically ill. We are designing and synthesizing novel analogues of etomidate with reduced capacity to suppress adrenocortical function, studying these agents using computer modeling, in vitro receptor and cellular systems, and rodent models. We have designed some of these agents to be ultra-rapidly metabolized by nonspecific esterases and very short-acting, similar to remifentanil and esmolol. We have designed others not to bind to 11beta-hydroxylase. Additional details of this aspect of our work can be found in recent published reviews (e.g. Br J Anaesth. 2010 Sep;105(3):246-54 and Chemical & Engineering News 2011 Aug;89(34):13-20).
In collaboration with Dr. Fumito Ichinose, the lab is also developing and studying novel drugs to prevent or treat neurological disorders, including ischemic stroke and dementia. These drugs are designed to both inhibit NMDA receptors and release hydrogen sulfide gas.