164 
Active  Principle  of  Ergot. 
Am.  Jour.  Pbarm. 
April,  1911. 
the  toxicity  of  ergotoxin  and  hydroergotinin  differed  too  much  for 
them  to  be  the  same  compound.  Meulenhoff  had  a  similar  experi- 
ence but  his  experiments  may  be  objected  to  on  the  ground  that  he 
was  not  using  the  purest  products  of  these  investigators. 
The  intravenous  injection  of  .0005  to  .001  gram  of  ergotoxin 
into  a  pithed  cat,  under  artificial  respiration,  caused  persistent  rise 
in  the  systemic  blood  pressure,  without  a  preliminary  fall.  Dale 
noted  that  after  such  an  injection  adrenalin  failed  to  cause  an  imme- 
diate rise  in  blood  pressure  and  showed  what  he  called  a  "  reversal 
in  action,"  that  is,  a  fall  in  blood  pressure.  In  doses  of  a  few  milli- 
grams, ergotoxin  produced  the  typical  bluing  of  the  cock's  comb  and 
the  uterine  contractions  in  pregnant  animals  characteristic  of  ergot. 
The  injection  of  2  mg.  of  ergotoxin  dissolved  in  dilute  NaOH,  into 
the  ear  vein  of  a  rabbit,  was  followed  in  one  case  by  dry  gangrene 
of  the  ear.  Unlike  Robert's  cornutine,  it  produced  no  convulsions 
in  frogs. 
Barger  and  Dale  at  first  believed,  as  did  Kraft,  that  the 
active  alkaloid  was  a  hydrated  form  of  the  inactive  one,  and  they 
adopted  Kraft's  view  that  each  base  could  be  converted  into  the 
other  at  will.  The  transformation  of  the  inactive  alkaloid  into 
an  active  form  was  supposed  to  be  accomplished  by  heating  in  dilute 
phosphoric  acid.  A  more  careful  study  has  shown  that  this  process 
does  not  yield  ergotoxin  phosphate,  as  was  originally  supposed,  but 
a  phosphate  of  ergotoxin-ethyl-ester.  This  has  some  physiological 
activity,  so  that  in  working  with  such  solutions  one  is  apt  to  be 
misled  in  attributing  the  action  to  this  base.  Ergotoxin  thus  con- 
tains a  carboxyl  group  and  the  relation  between  the  inactive  and 
active  alkaloids  is  that  of  a  lacton.  Barger  and  Dale  believe  the 
basic  bodies  isolated  by  Keller  and  also  by  Dragendorff  to  be  mixtures 
of  inert  ergotinin  with  ergotoxin. 
They  soon  noted  that  all  of  the  physiological  activity  of  ergot 
could  not  be  explained  on  the  basis  that  ergotoxin  was  the  sole 
active  principle,  but  that  there  must  be  some  water-soluble  one 
to  which  most  of  the  activity  of  ergot  was  due.  In  investigating  the 
pressor  action  of  putrid  meat  Barger  and  Walpole  found  it  was  due 
to  p.  oxyphenylethylamin, 
HO<ZZI>CH2CH2NH2,  isoamylamin,  ^^^^  >CH,  CH^NHj, 
and  phenylethylamin,  and  at  once  suspected  some  of  these  bodies 
to  be  the  missing  principles  in  ergot.    They  found  p.  oxypheny- 
