A™'ctJo^iP9lo"m"}  Cardiac  Stimulants  and  Depressants.  461 
as  their  activity  is  largely  dependent  upon  their  alkaloidal  content. 
Although  aconite,  gelsemium  and  veratrum  contain  alkaloids  upon 
which  their  activity  depends,  their  physiologic  strength  does  not 
necessarily  nor  invariably  vary  in  accordance  with  their  alkaloidal 
content.  The  physiologic  activity  of  aconite  is  mainly  due  to  the 
aconitine  which  it  contains,  but  this  alkaloid  contains  in  chemical 
combination  a  methyl  and  a  benzoyl  group,  either  of  which  may 
be  split  off  during  the  handling  of  the  drug  and  the  loss  of  which 
renders  the  aconitine  inactive,  while  still  permitting  it  to  respond 
to  the  chemical  reactions  of  an  alkaloid.  This  is  particularly 
prone  to  occur  on  long  standing  of  its  preparations.  Veratrum 
contains,  in  addition  to  veratrine,  a  series  of  alkaloids,  among 
which  may  be  mentioned  protoveratrine,  veratroidine  and  proto- 
veratridine,  which  are  almost  entirely  inactive,  but  which  cannot 
be  easily  distinguished  chemically  from  the  active  alkaloids. 
Gelsemium  contains  two  alkaloids,  gelsemine  and  gelseminine,  the 
former  of  which  has  practicallv  no  effect  on  mammals  but  cannot 
well  be  distinguished  by  any  chemical  assay  process.  On  account 
of  the  possibility,  therefore,  of  obtaining  misleading  results  from 
chemical  assay  alone,  we  are  reduced  to  the  necessity  of  sub- 
stantiating such  assays  by  physiologic  means.  Conium,  physostigma, 
and  lobelia  all  contain  alkaloids  upon  which  their  pharmacologic 
and  therapeutic  activity  depends,  and  the  amount  of  which  gives  a 
direct  indication  of  the  therapeutic  activity  of  the  product.  It  is 
therefore  not  considered  necessary  to  standardize  these  products 
physiologically. 
After  a  large  number  of  experiments  extending  over  several 
months,  the  following  standards  have  been  adopted  for  the  three 
drugs  first  mentioned.  In  each  case  the  amount  mentioned  is  injected 
subcutaneously  into  a  guinea  pig,  and  other  pigs  are  given  respectively 
9/10  and  11 /i0  of  the  standard  dose.  If  all  three  of  these  doses 
prove  fatal,  a  smaller  dose  is  given  to  a  fresh  pig ;  if  none  prove 
fatal,  a  larger  dose  is  given  to  a  fresh  pig.  If  the  dose  given  in 
the  table  proves  fatal  within  three  hours,  and  the  pig  receiving 
9/10  of  this  lives  longer  than  this  period,  the  drug  is  considered  to 
be  of  standard  quality.  The  doses  given  in  the  table  are  based 
on  250  gramme  pigs  and  in  case  the  pig  weighs  more  or  less 
than  this  amount,  are  made  proportionate  to  its  weight.  The 
dosage  is  given  in  grammes  of  the  drug  and  extract  and  in  cubic 
centimetres  of  the  liquid  preparations, 
