436  Specificity  of  Drugs  for  Phosphatids.  {^oiXrf!?™" 
dominant  physiological  effect  this  is  the  result  of  a  correspondingly 
large  chemical  alteration.  A  small  amount  of  a  drug  in  one  tissue 
may  produce  a  much  more  noticeable  pharmacological  effect  than  a 
large  quantity  in  another  group  of  cells.  Data  is  continually  accu- 
mulating which  shows  that  some  chemical  compounds,  as,  for  in- 
stance, the  hypnotics  and  anesthetics,  are  selected  by  the  various 
tissues  in  approximate  accordance  with  their  lipin  content. 
The  phosphatids  of  the  brain  may  be  concerned  in  the  action  of 
brain  drugs  in  one  or  more  of  several  ways :  ( I )  There  may  be  a 
more  or  less  firm  physical  or  chemical  combination  between  the 
drug  and  the  phosphatid  in  the  cell  itself.  This  might  interfere 
with  the  normal  respiration,  as  there  is  evidence  for  believing  in 
the  case  of  anesthetics.  The  phosphatids  are  very  likely  concerned 
in  the  metabolism  of  cell  food,  so  the  drug  might  affect  this  process. 
(2)  The  drug  may  enter  into  combination  of  some  sort  with  the 
extremely  complex  associations  of  lipoids,  proteins,  salts,  etc.,  that 
very  probably  exist  in  the  cell.  In  this  case  the  effects  produced 
might  be  similar  to  those  given  above,  but  there  might  be  no  direct 
effect  of  drugs  on  the  lipins  themselves.  (3)  Whatever  the  nature 
of  the  limiting  surface  layer  of  the  cell,  the  phosphatids  in  it, 
through  solution  of  the  drug,  adsorption  of  it,  or  chemical  combina- 
tion with  it,  may  bring  about  a  specific  transference  of  this  par- 
ticular drug  to  the  interior  of  the  cell  and  there  cause  disturbance 
in  normal  activity  by  affecting  compounds  probably  other  than  phos- 
phatids. If  it  is  a  question  of  solution-permeability,  then  one  would 
expect  that  the  specificity  would  depend  very  largely  on  the  locali- 
zation and  quantity  of  the  lipin  and  not  so  much  on  its  chemical 
nature.  (4)  Or  the  phosphatids  may  interfere  with  the  passage  in 
and  out  through  this  surface  layer  of  food  or  metabolized  products. 
This  might  lead  to  a  more  or  less  general  cell  asphyxiation  or  cell 
starvation  in  the  former  case,  while  in  the  latter  we  would  have 
so-called  toxic  effects,  resulting  from  accumulations  of  end  products 
which  would  cause  retardation  (depression)  or  increase  (stimula- 
tion) of  the  rate  of  metabolism. 
The  same  possibilities  apply  to  the  action  of  heart  drugs  on  heart 
phosphatids. 
It  is  rather  difficult  to  understand  just  how  a  drug  could  pro- 
duce changes  in  physico-chemical  properties3  without  altering  to 
some  extent  the  chemical  nature  of  the  substances  present.  It 
3  Handowskay,  Biochem.  Z.,  25,  510,  1910. 
