The depressing effect of the narcotic would then consist in producing incapability of the lipoids transmitting oxygen to act as carriers of the same, and it is, therefore, self-evident that the effect of the narcotic would be the stronger the more readily it found entrance into the lipoids. It is perhaps not without interest that in similar manner Mansfeld[229] has attempted to establish a connection between the facts which Meyer and Overton have found and those ascertained by my coworkers and myself. He expressed the view that the lipoids of the cells represent the channels followed by the oxygen on its entrance, and that in consequence of their accumulation in the lipoids, the narcotics bring about asphyxiation by physically obstructing the transmission of the oxygen from the outer medium through the surface layer of the lipoid into the protoplasm. The divergence in our views is not essential in their nature, and I attach the less importance to them as we find ourselves here, as I must again emphasize, on purely hypothetical ground.
In consideration of these observations we may perhaps establish the following hypothesis of the effect of the oxydative suppression of narcotics: The narcotics obstruct, either by absorption or loose chemical combination the oxygen carriers of the cell and render them incapable to activate the molecular oxygen. In consequence, oxydation of the oxydable substances cannot take place and disintegration occurs of an anoxydative form. The cell asphyxiates.
In conclusion I wish to warn against erroneous assumption that all oxydative depressions by chemical substances are narcosis and that the mechanism is the same. It is true that a number of chemical substances depress the processes of oxydation. But the latter can be brought about in very varying ways. I would like to mention the effect of oxydative depression of aldehydes. To this Warburg[230] has added hydrocyanic acid, arsenic acid, ammonia and substitution compounds of ammonia. These substances do not follow the Meyer-Overton law of the coefficient of distribution. We cannot consider them, therefore, as narcotics. Future investigation will establish the existence of a large number of substances belonging to this great group of oxydation suppressing poisons, which are not narcotics. And it is likewise certain that depressing substances will be found, the depressing effects of which will not have their point of attack in the oxygen exchange, but will be shown to exist in other constituents of the metabolic chain. Our research in these fields, as already said, is still in the first beginnings and its perspective reaches into infinite space.
FOOTNOTES:
[1] Franciscus Glissonius: “Tractatus de natura substantiæ energetica seu de vita natura ejusque tribus primis facultatibus perceptiva, appetitiva, motiva,” etc. Londini M D C L XXII.
[2] Franciscus Glissonius: “Tractatus de ventriculo et intestinis cui præmittitur alius de partibus continentibus in genere et in specie de iis abdominis.” Amstelodami M D C L XXVII.
[3] Albrecht v. Haller: “Elementa Physiologiæ corporis humani.” Tomus IV. Lausannæ M D C L XVI.
[4] John Brown: “Elementa medicinæ.” 1778. English translation. London 1778.
[5] Johannes Müller: “Über die phantastischen Gesichtserscheinungen. Eine physiologische Untersuchung mit einer physiologischen Urkunde des Aristotles über den Traum, den Physiologen und den Arzten gewidmet.” Coblenz 1826.
[6] Johannes Müller: “Handbuch der Physiologie des Menschen für Vorlesungen.” Coblenz 1837.