The mysteries of anesthesia uncovered

Paris, May 6, 1999

Inhalational anesthetics haved been used in surgery for over 150 years. Yet, until now, the mechanisms governing anesthesia were practically unknown. The recent findings of a team from the Institute of molecular and cell pharmacology of the CNRS in Sophia-Antipolis have greatly improved our knowledge in this field. This team specializes in the study of ionic channels, biological macromolecules which generate the electrical signals whereby the cells of our nervous system communicate with each other and with other organs of the body. In an article published in the May issue of Nature Neuroscience, the researchers describe how one of these ionic channels, receptive to potassium, is targeted by general inhalational anesthetics.

Although ether and chloroform are no longer used as general anesthestics in developed countries, other inhalational anesthetics still are. These are fluoride compounds (halothane, isoflurane, enflurane, sevoflurane, desflurane). They are much more effective and have fewer side-effects. These inhalational anesthetics represent a very important class of drugs. Their properties are extremely interesting: they provoke a loss of consciousness, and a partial loss of memory, since the memory of the surgical operation is erased. The body becomes motionless but still reacts to painful stimuli.

A great deal of progress has been made in the field of anesthesia during the past decades, even though the actual mechanism of the molecules used for that purpose were not really understood. The researchers of the Institute of molecular and cell pharmacology of the CNRS in Sophia-Antipolis, -— Amanda Patel, Eric Honoré, Florian Lesage, and Georges Romey, headed by Michel Lazdunski, — have just made several important discoveries. They have found that one of the ionic channels, receptive to potassium is targeted by inhalational general anesthetics. These channels play a crucial role in the control of the relaxation potential of nervous cells in the brain and in the spinal cord. They are present in the neurons which play a part in memorization and in motor activities. General anesthetics open up these channels and hyperpolarize the nervous cells, preventing the neuron network from functioning normally. The opening of the channels by general anesthetics slows down the action and communication potential of neurons generated by neurotransmitters.

This discovery not only revealed a physiological phenomenon which had so far remained mysterious, but may also lead to the development of new anesthetic agents which are increasingly similar to what would be the ideal anesthetic. This anesthetic would have the following properties: it would 1) induce anesthesia rapidly and pleasantly 2) make possible the control the degree of anesthesia, 3) induce adequate muscular relaxation, 4) reduce the risks of anesthesia-induced accidents, 5) be devoid of toxic or side effects.

A SHORT HISTORICAL BACKGROUND
Ether was used for the first time in 1842 by Crawford Long, in Jefferson, U.S.A.; the first public demonstration of the use of ether as an anesthetic was made by the dentist William Morton in 1846, at the Massachusetts General Hospital in Boston. Morton first became interested in anesthesia for the purposes of dental extraction. Then, on October 16, 1846, he used ether for the painless extraction of a neck tumor, without revealing the nature of this miraculous anesthetic agent which he called Letheon. He planned to patent his discovery, but before he managed to do so the medical and scientific community found out that this miracle drug was ether. Within several weeks, the use of ether as an anesthetic became common practice throughout the United States and Europe. Morton thus never succeeded in patenting “his” discovery.
Chloroform was first introduced in the United States in 1847. Anesthesia was developed as a separate medical practice by two Englishmen, Joseph Clover and John Snow. The latter became famous in this field for having performed chloroform anesthesia on Queen Victoria in 1853, when she gave birth to prince Leopold. Clover became famous for the invention of inhalators, thanks to which one can determine precise dosages of ether or chloroform, according to need. These discoveries marked the beginning of anesthesia as a separate medical discipline.

Reference
Patel A.; Honoré E., Lesage F., Fink M., Romey G., Lazdunski M.- Inhalational Anaesthetics are activators of two pore domain background K+ channels, Nature Neuroscience, May 1999.

Researcher Contact
Michel Lazdunski
Directeur de l’Institut de pharmacologie moléculaire et cellulaire (CNRS – Sophia Antipolis – Valbonne)
Tel: 33 4 93 95 77 03
Fax: 33 4 93 95 77 04

Press contacts
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Communication du département des sciences de la vie
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