This section is from the book "Materia Medica: Pharmacology: Therapeutics Prescription Writing For Students and Practitioners", by Walter A. Bastedo. Also available from Amazon: Materia Medica: Pharmacology: Therapeutics: Prescription Writing for Students and Practitioners.
As the remedies which depress the central nervous system regularly depress the cerebrum, they are known generally as narcotics, a narcotic being a remedy which tends to produce a depressed state of consciousness. Consciousness is a function of the cerebral cortex. The rapidity of the onset of narcosis varies greatly with the different narcotics, but the degree of narcosis increases in a regular way with the amount given. Slight narcosis, for example, shows merely in a tendency to quietness, while greater degrees show in succession drowsiness with mental and physical sluggishness, then sleep, not quite like the natural sleep, then stupor, and finally loss of consciousness (coma). Stupor, or torpor, is a condition of unconsciousness or semiconsciousness from which one can be aroused, but with difficulty; and coma, a condition of unconsciousness from which one cannot be aroused.
1. The Meyer-Overton, which was propounded by Meyer and Overton independently. It is that these drugs exert their main action on the central nervous system, because they are taken up by the fats and lipoids which abound there, and so are held in considerable amount in contact with the cell structures. The lipoids are lecithin, cholesterin, cerebrin, protagon, etc. According to these authors, the anesthetic property increases with the solubility in fats and lipoids and the insolubility in water. The relation of the activity of hypnotics and anesthetics to their solubility in lipoids is certainly a striking one, and there is a very large amount of evidence supporting this theory, which is the one most generally accepted. It, of course, merely indicates how the anesthetic gets to the nerve-cell, and not what takes place in the cell.
They believe that narcosis or anesthesia is due to a change in the protoplasm of the cerebral cells by the formation of loose compounds of ether, chloroform, etc., with the cell proteins, and that this results in limitation of the activities of the cerebral protoplasm. On account of the instability of the compounds, these remain formed only so long as the vapor-pressure of the anesthetic in the blood is maintained; so on stopping the administration of the anesthe tic the narcosis soon ceases. In the words of Moore and Roaf, "that a certain amount of the anesthetic will be taken up by the lipoid in a physical fashion there can be no doubt, because of the high solubility of these anesthetics in such lipoid substances. But we hold that the portion of the anesthetic so taken up and held by the lipoid is passive and not active, and that it is the portion taken up by the protein which is active in paralyzing protoplasmic activity and producing anesthesia. It is a matter of common knowledge that the greater the amount of fatty tissue in a subject undergoing anesthetization, the greater is the amount of anesthetic required. The portion of anesthetic absorbed by the lipoid is imprisoned, and more anesthetic must be given in order to raise the (vapor) pressure of the anesthetic sufficiently to cause combination between cell protoplasm and anesthetic, with resulting anesthetization."
The one theory assumes that the ether dissolved in the fats and lipoids is the anesthetic ether; the other considers this ether lost or imprisoned, and the anesthetic ether to be only that which enters into combination with the cell proteins.
He accepts the Meyer-Overton theory as showing the properties necessary for an anesthetic to reach the field of action. But he goes on to give an explanation of the cause of the depression of the activity of the cerebral cells. He shows that in narcosis there is interference with the oxidative processes of the cells, or, in his own words, "the factor which produces the characteristic symptom-complex of narcosis is under all circumstances the suppression of the power to carry on oxidations." His theory is that narcotics render the oxidases (the oxygen carriers) in living tissues incapable of carrying oxygen. He shows that this may take place in any cells of the body, but that the cells of the cerebral cortex are especially sensitive to lack of oxygen, and are depressed with very much less of the narcotic than is necessary to depress the nerves and muscles.
One of his experiments may be cited: The sciatic nerve of a frog was deprived of oxygen until its irritability was much reduced and its conductivity lost. It was then narcotized with ether. During the ether, oxygen was supplied for a long time, but it had no effect whatever upon the narcosis. Then nitrogen was substituted for the oxygen, and the narcotic was stopped. Still, though the ether passed off, the functions were not restored in the nitrogen atmosphere. After a while the nitrogen was replaced by air, and in one minute the nerve had recovered its conductivity and its irritability. That is, so long as the cell was under the narcotic influence, oxygen had no power to set the cell functionating, but did set it functionating when the narcotic had been removed. Also the mere removal of the narcotic was not enough, but oxygen was necessary to restore the lost functions of the cell.
In opposition to this theory is the demonstration by Winter-stein that intestinal parasites keep alive and active in unoxygen-ated fluids, yet respond by narcosis to alcohol and chloroform; and the demonstration by Loeb and Wastenys that in certain low forms profound narcosis can be induced without any noteworthy diminution of the normal rate of oxidation, and that in order to depress oxidation a narcotic must be given in far greater concentration than is required for narcosis.