Am.  Jcmr.  Pharm. ) 
May,  1911.  / 
Standardisation  of  Digitalis. 
209 
All  lethal  dose  methods  are  objectionable,  because  they  offer 
nothing  characteristic.  The  fact  that  a  given  preparation  is  capable 
of  killing  an  animal  is  certainly  no  proof  of  its  therapeutic  value. 
The  active  glucosides  of  digitalis  may  become  decomposed  into  such 
bodies  as  digitalresin  and  toxiresin,  which,  resembling  picrotoxin, 
have  a  depressant  action  on  the  heart,  and  a  preparation  containing 
a  large  amount  of  such  decomposition  products,  while  testing  high 
by  lethal  dose  micthods,  might  not  only  be  below  standard,  but 
capable  of  causing  dangerous  poisoning.  On  this  account,  Hough- 
ton's method  is  open  to  criticism.  Still  less  satisfactory,  however, 
is  fthe  guinea-pig  method,  for,  in  addition  to  being  only  a  lethal 
dose  method,  the  animal  probably  always  dies  from  the  action  of 
the  drug  on  the  central  nervous  system.  As  Edmunds  and  Hale  ^ 
put  it,  "  One  solution  might  be  very  weak  in  its  action  upon  the 
heart  and  yet  contain  decomposition  products  of  digitalis  whose 
typical  action  is  upon  the  medulla,  and  it  would,  therefore,  appear 
unduly  strong  when  judged  by  such  a  standard.  For  this  reason, 
we  think  that  methods  which  employ  as  a  standard  the  minimum 
lethal  dose  upon  the  higher  animals  are  not  applicable  to  the 
physiological  assay  of  digitalis  series." 
It  is  in  this  respect  that  the  one-hour  and  Focke's  methods  are 
much  superior.  In  both  of  these,  the  condition  of  the  heart  is  taken 
as  a  criterion.  That  this  action  on  the  heart  occurs  before  the 
death  of  the  animal. is  shown  by  the  not  uncommon  observation  of 
frogs  able  to  crawl  around  and  very  much  alive  but  whose  hearts 
present  the  characteristic  "  digitalis  "  picture  when  the  thorax  is 
opened ;  a  picture  produced  by  no  drug  with  which  I  am  acquainted 
except  digitalis  and  its  allies.  I  am  convinced  that  such  animals 
as  these  would  recover  from  the  intoxication  produced  by  digitalis 
if  they  were  not  molested  and  the  point  should  be  emphasized  thai 
these  "  frog  heart  "  (Focke's  and  the  one-hour  method)  methods  are 
not  lethal  dose  methods.  Focke's  method  is  rather  complicated  and 
the  fact  that  it  necessitates  opening  the  thorax  of  an  unpithed  frog 
should  prevent  its  adoption. 
That  the  two  "  frog  heart  "  methods  are  accurate  within  10 
per  cent,  is  admitted.  The  cost  is  a  feature  that  must  be  considered 
in  any  commercial  method  of  assay,  and  a  dozen  frogs  can  be 
purchased  for  the  same  amount  as  one  guinea-pig ;  thereby  enabling 
many  more  control  experiments  with  frogs  for  the  same  monetary 
expenditure  for  material. 
