STUDY OF THE PHYSICAL CHEMISTRY OF ANAESTHESIA 
however, does nothing towards elucidating what happens when these substances do 
enter the cell, nor is there any proof that diffusion into the cell is difficult for such 
substances, but rather the reverse is true, for the facts of the rapid onset and recovery 
from anaesthesia show that they enter and leave the cell quite freely and rapidly. 
With regard to the statement that in such a large number of cases the anaes- 
thetic is not only less soluble -in water but also more soluble in olive oil, it may be 
pointed out, that in the vast majority of the substances experimented with the sub- 
stances are soluble in all proportions in olive oil, and hence no comparison is possible. 
Secondly, it is a general rule in the case of all organic substances of the classes 
under consideration, that the less soluble they are in water the more soluble they are 
in organic substances, which, like themselves, are insoluble in water. 
For example, if a given organic substance has a low solubility in water and a 
high solubility in, say, ether, in the great majority of cases it will also have a high 
solubility in chloroform, benzol, xylol, toluol, and the oils and fats, viz., in substances 
which have themselves a very sparing solubility in water. 
Finally, it may be mentioned that the lipoid theory does not at all fit the experi- 
mental facts in the case of the basic anaesthetics', or narcotics, which belong to the 
class of bodies known as alkaloids, such, for example, as coniin, nicotin, and morphia. 
For this class of compounds, Overton 2 admits the existence of combinations, probably 
of the nature of salts between the basic anaesthetic and the tissue proteids, and it is 
strange that this should not have suggested determinations of the action of proteids 
upon the so-called ' indifferent ' anaesthetics, which would have at once demonstrated 
that these form similar compounds, as is shown by the experiments detailed below. 
It hence becomes an advantage of the theory which refers the causation of anaes- 
thesia to the formation of unstable combinations between the anaesthetic and the cell 
protoplasm, that it furnishes a common explanation of the action of all types of anaes- 
thetic whether basic or indifferent. 
A basis is also provided for an explanation of the difference in rate of recovery 
from the anaesthesia in the case of the different anaesthetics, and for the selective action 
of certain anaesthetics. For it is obvious that such factors will have an influence as 
the stability and dissociation pressure of the combination between the anaesthetic and 
the protoplasm, as well as the rate of diffusion into and out of the cell, in determining 
the rate of intake and output of the anaesthetic, and hence of the onset and subsidence 
of the anaesthesia. Further, there must exist differences in the composition and state 
of aggregation of the proteid molecules going to build up the protoplasm in the case 
of different classes of cells, and hence facility or the reverse for combination with 
different chemical compounds or anaesthetics must exist, so that one alkaloid will 
accordingly pick out and combine with the organized proteid of one type of cell, 
i. There are also certain exceptions in the case of the so-called indifferent anaesthetics. 
2. StuJien uber die Narkose, S. 1 60, et seq. 
