Mystery of anesthetic mechanism may be solved

by MIKE MARTIN, UPI Science Correspondent

NEW YORK, Feb. 15, (UPI) -- Although more than 150 years have past since the discovery of general anesthetics, how they precisely work remains a mystery. Biophysicists at the Mount Sinai Medical Center in New York may be close to solving this riddle.

Huping Hu and Maoxin Wu have proposed a mechanism that may lead to better, safer anesthetics, a revolution in the treatment of pain, and a more complete understanding of the effects of alcohol on brain function. General (as opposed to local) anesthetics affect a variety of neurotransmitter receptors.

However, a universally accepted mechanism of anesthesia remains elusive. Presently, two schools of thought exist. The "lipid theory" proposes that anesthetics interact directly with cell membranes that are involved in brain functions. The "protein theory" suggests that anesthetics directly interact with cell proteins such as the ion channels and receptors that are involved in neurotransmission. Neither concept is supported by direct experimental evidence.

Wu and Hu, on the other hand, speculate that general anesthetics perturb the pathways of oxygen, the most essential component of brain function, in both cellular membranes and cellular proteins. In essence, their mechanism holds that anesthetics act as barriers to oxygen transport in both membranes and proteins, reducing oxygen availability to the brain. When the brain detects oxygen deprivation, or hypoxia, it immediately reduces its workload. Part of this workload is sensing pain. Wu and Hu claim that anesthesia, then, is a byproduct of the brain's own self-preservation mechanism.

Wu and Hu predict that better anesthetics can be formulated that more effectively block oxygen pathways by enhancing their ability to be absorbed by the fatty membranes that serve as oxygen gateways. Anesthetics with shorter hydrocarbon chains would be more effective than anesthetics with longer-chain hydrocarbons because the membranes that control oxygen uptake in the brain more easily absorb them. Additionally, clinicians may use the proposed mechanism to better control and predict side effects.

"Anesthesiologists need consider direct monitoring of intracellular or even sub-cellular oxygen concentrations during anesthetic procedures since our hypothesis suggests hypoxia or hypoxia-mimicking situations at the sub-cellular or molecular level," Dr. Hu told UPI. Too much oxygen deprivation at this level can lead to tissue death, he said.

Dr. Judith Tharp, a chief clinician with the Federal Bureau of Prisons, expressed fascination with the results. "There's no question that a mechanism such as the one proposed by Drs. Wu and Hu could result in the formulation of better anesthetics, simply by defining their exact targets more precisely," she said. "It is true--we still don't know exactly what we are aiming for with general anesthesia."