Biophysicists in New York may be close to solving the riddle of how general
anesthetics actually work.
Researchers Maoxin Wu and Huping Hu suggest anesthetics act as barriers
to oxygen transport in both membranes and proteins, reducing oxygen availability
to the brain. Their mechanism 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.
Wu and Hu, both pathologists, are with Mount Sinai Medical Center, New
York, and Biophysics Consulting Group, Old Bethpage, New York, respectively.
Although more than 150 years have past since the discovery of general anesthetics,
how they precisely work remains a mystery. While scientists know general
anesthetics affect a variety of neurotransmitter receptors, a universally
accepted mechanism of anesthesia remains elusive.
Two
schools of thought have existed until now:
-- 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, however.
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.
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 further research could formulate better anesthetics that
more effectively block oxygen pathways by enhancing their ability to be
absorbed by the fatty membranes that serve as oxygen gateways. For example,
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, alcohol's intoxicating effects may result from disruption
of oxygen pathways in the brain, and many side effects of general anesthetics,
including some well-known but poorly understood toxicities, may be explained
by the proposed mechanism. Short-chain hydrocarbon anesthetics, for instance,
have fewer and less toxic side effects and they are better oxygen blocks.
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."
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Copyright
2001 by United Press International.
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