Am.  Juur.  Pliarm.  1 
August,  1910.  j" 
Standardization  of  Drugs. 
367 
digitonin  of  which  it  is  chiefly  composed.  German  digitalin  prob- 
ably has  no  place  in  digitalis  therapy. 
When  the  official  preparations  of  digitalis,  such  as  the  tincture, 
are  diluted  with  water  a  precipitate  occurs,  indicated  by  a  faint 
opalescence,  and  in  our  earlier  experiments  we  were  unable  to  get 
uniform  results  when  these  diluted  liquids  were  injected  over  a  period 
of  an  hour  or  more.  The  injection  of  a  large  amount  of  alcohol  is 
not  permissible,  and  the  use  of  concentrated  preparations  precludes 
the  same  degree  of  accuracy  that  is  possible  with  the  more  dilute 
liquids.  These  objections  are  overcome,  in  part,  by  the  combined 
method,  in  which  ouabain  is  used  to  complete  the  estimation. 
AYe  have  never  seen  any  embarrassment  of  the  respiration  be- 
yond some  increase  in  the  rate  until  the  heart  stopped.  The  immedi- 
ate signs  of  asphyxia  with  excessive  efforts  at  respiration  showed 
that  the  respiratory  centre  was  still  intact.  Furthermore,  those 
drugs  which  kill  by  paralysis  of  the  respiratory  centre,  usually  give 
very  variable  results  when  used  in  this  way.  Strychnine  is  an  ex- 
ception, but  there  are  many  factors  involved  in  the  rapid  action  of 
strychnine,  and  it  is  quite  possible  that  the  sudden  death  following 
the  intravenous  injection  is  not  due  to  its  direct  effects  on  the  res- 
piratory centre  alone.  The  fact  that  the  heart  stops  after  all 
of  the  digitalis  bodies  before  the  respiration  is  seriously  impaired 
is  the  strongest  answer  we  can  make  to  the  contention  of  Edmunds 
and  Hale  (Hygienic  Laboratory,  Bulletin,  No.  48,  1908),  that 
methods  which  employ  as  a  standard  the  minimum  lethal  dose  for 
the  higher  animals  are  not  applicable  to  the  physiological  assay  of 
the  digitalis  series. 
It  is  hardly  necessary  to  state  that  it  is  a  matter  of  vital  im- 
portance that  a  standard  shall  be  found  for  all  the  digitalis  bodies  in 
which  the  relative  activity  of  the  different  members  on  the  human 
heart  may  be  expressed. 
Hale  found  between  7  and  8  mgs.  of  digitoxin  per  kg.  of  frog, 
and  600  mgs.  of  digipuratum  per  kg.  (/.  Am.  Med.  Assn.,  v.  54, 
p.  129)  necessary  to  cause  systolic  standstill  in  an  hour.  This  is 
sixteen  times  the  amount  of  digitoxin,  and  eight  times  the  amount 
of  digipuratum,  required  per  kilo  for  the  cat's  heart  in  our  experi- 
ments. On  the  other  hand,  wre  have  found  less  than  twice  as  much 
strophanthus  is  required  per  kilo  of  frog  as  for  the  cat. 
The  following  figures  expressed  in  milligrammes  per  kg.  of 
frog  were  obtained  by  Famulener  and  .Lyons  (Proc.  Am.  Ph.  Assn., 
