^™Maix*h  ■  mr"^' }  Biological  Standardisation  of  Drugs.  105 
together  in  the  following  table  not  only  as  a  means  of  comparing 
the  activities  of  the  various  so-called  pure  principles  but  also  to 
show^,  in  tabular  form,  the  amount  of  error  which  is  to  be  expected 
when  using  a  frog-heart  method  of  assay. 
Drug  Assay  Value  ^  Unknown  Solutions  per  cent,  error. 
1910 
1902  ^ 
I 
2 
3 
4 
Strophanthin 
0.000,001,10 
0.000,000,5 
1.8 
2.9 
3-1 
1.4 
Convallamarin 
0.000,004,75 
0.000,004,5 
8.6 
10.6 
74 
9.0 
Digitoxin 
0.000,008,50 
0.000,008,5 
7.2 
3.8 
0.7 
5-2 
French  Digitalin 
0.000,013,00 
0.000,015 
1.6 
3-8 
3.6 
2.6 
Digitalein 
0.000,024,00 
0.000,032,5 
4-5 
3-8 
6.0 
1.5 
German  Digitalin 
0.000,070,00 
0.000,022,5 
2.5 
2.8 
5-9 
0.0 
From  this  summary  it  is  apparent  that  strophanthin  is  the  most 
active,  the  German  digitalin  (Digitalin  purum  Griibler)  is  the 
weakest  and  that  digitoxin  the  most  active  of  the  digitalis  glu- 
cosides,  is  about  8  times  less  active  than  amorphous  strophanthin. 
It  is  not  urged  on  the  basis  of  these  experiments,  however,  that 
in  the  clinical  use  of  these  substances  doses  be  given  proportionate 
to  these  values.  But  in  so  far  as  secondary  factors,  such  as  rate 
of  absorption  and  elimination,  do  not  interfere  proportionate  doses 
would  probably  give  like  therapeutic  results.  Elemental  tissues 
such  as  the  heart  muscle,  no  matter  from  what  animal  species, 
react  qualitatively  the  same.  As  pointed  out  by  Cushny  *  the 
action  of  the  digitalis  group  upon  the  frog's  heart  is  strictly  anal- 
ogous to  the  action  on  the  mammalian  heart  with  differences  in 
action,  dependent  upon  a  stronger  vagus  activity  in  the  higher 
animal  species.  In  the  therapeutic  use  of  the  drug  only  the  first 
stage  which  consists  of  a  minimal  activity  of  the  vagi  and  a 
definitely  increased  activity  of  the  muscle  substance  itself  is  desired. 
The  action  on  the  frog  is  almost  purely  a  muscle  action  and  it  is 
upon  such  grounds  that  biological  assay  methods  on  the  lower 
forms  of  animal  life  are  believed  to  give  results  which  are  capable 
of  direct  utilization  in  therapeutics. 
On  theoretical  grounds,  therefore,  there  is  no  reason  why  assays 
using  frogs  will  not  give  results  which  may  not  be  depended 
^Amount  in  gram  per  gram  body  weight  of  Rana  pipiens  to  cause 
permanent  systole  of  the  ventricle  in  one  hour. 
^  Famulener  and  Lyons. 
*  Cushny :  Pharmacology  and  Therapeutics,  1906,  p.  466. 
