970 



SCIENCE 



[N. S. Vol. XXXVII. No. 965 



ity, and the injurious action of the pure 

 NaCl is relatively slight. Bringing larvas 

 from normal sea water directly into ether- 

 containing NaCl solution also causes little 

 or no stimulation or loss of pigment, and 

 the cilia and body cells are protected 

 against the injurious action of the solution. 

 Thus in the presence of the anesthetic the 

 salt solution fails to show its normal stimu- 

 lating and permeability-increasing action, 

 and its toxic or cytolytic action is greatly 

 diminished. Anti-stimulating and anti- 

 cytolytic actions run parallel with each 

 other. 



I have studied the action of a large num- 

 ber of anesthetics in this manner. Those 

 which promptly and completely anesthetize 

 Arenicola larvee in sea-water show, when 

 dissolved in NaCl solution in the proper 

 proportions, effects which are essentially 

 identical with those just described, though 

 varying in degree with the different anes- 

 thetics. Alcohols (methyl, ethyl, propyl, 

 butyl, amyl, capryl),theurethanes (methyl, 

 ethyl, phenyl), other esters like ethyl ni- 

 trate, acetate, propionate, and compounds 

 like ehloretone, acetanilide, paraldehyde, 

 nitromethane, chloroform, acetonitrile, all 

 decrease or prevent the stimulating and 

 permeability-increasing action of pure 

 NaCl solutions when present in the con- 

 centrations which cause typical anesthesia 

 in sea-water. They also show well-marked 

 protective or anti-cytolytic action. Other 

 anesthetics, among which are chloral hy- 

 drate, benzol, phenyl urea, and chloralose, 

 act more slowly than those just mentioned, 

 and if larvas are brought suddenly into 

 their solutions in m/2 NaCl, stimulation 

 and loss of pigment occur very much as in 

 the pure salt solution. A parallelism be- 

 tween permeability-increasing action and 

 stimulating action is thus seen throughout. 

 If the one effect is decreased or prevented 

 so also is the other. 



The exact concentrations most favorable 

 for anesthesia and prevention of permeabil- 

 ity-increase are characteristic for each sub- 

 stance and have to be determined empiric- 

 ally. In a series of homologous compounds, 

 like the alcohols or the fatty acid esters, the 

 molecular anesthetic action increases rap- 

 idly with increase in molecular weight and 

 in lipoid-water partition-coefficient. The 

 same is true for the vertebrate central ner- 

 vous system, as Overton and Meyer have 

 shown. Overton's observations on tadpoles 

 show a close parallelism with my own in 

 these respects. The concentrations re- 

 quired to anesthetize Arenicola larvaj are, 

 however, higher in every case — usually 

 three to five times higher — than for tad- 

 poles. Possibly the higher salt content of 

 the tissue-media in marine animals is re- 

 sponsible for these differences ; the order of 

 relative action is the same in both organ- 

 isms. 



To sum up — it would thus seem that an- 

 esthetics produce their essential effects by 

 modifying the properties of the semi-per- 

 meable plasma-membranes of the irritable 

 tissues, making these structures more resist- 

 ant to changes of permeability than nor- 

 mally. Since variations of permeability 

 are essential to stimulation, the irritable 

 tissue is thus rendered temporarily insensi- 

 tive or irresponsive. 



How does the anesthetic produce these 

 effects ? Osterhout has recently shown that 

 anesthetics decrease the electrical conduc- 

 tivity of plant tissues, apparently by de- 

 creasing the permeability of the plasma- 

 membranes to ions ;'' and it may be that in 

 irritable animal tissues also the permeabil- 

 ity normal to the membranes is similarly 

 decreased during anesthesia. If the dis- 

 tinctive action of the anesthetics is to de- 

 crease permeability, its presence in the 

 tissue will naturally oppose increase of per- 



' Science, Vol. 37, 1913, p. 111. 



