296  Salts  of  Cantharidinic  Acid.  {Amj™e^9iarm 
Although  cantharides  has  been  employed  medicinally  since  the 
time  of  Hippocrates,  and  not  unfrequently  given  internally,  its  pow- 
erful influence  on  the  kidney  has  prevented  its  general  employment. 
It  has,  however,  been  recommended  in  several  ailments,  and  Lieb- 
reich  points  out  that  by  Cazenave,  Rayer,  and  other  French  derma- 
tologists, the  tincture  has  been  employed  in  psoriasis  and  chronic 
eczema,  in  doses  as  high  as  sixty  drops,  without  evil  results. 
A  consideration  of  the  influence  exerted  by  cantharides  on  the 
tissues  led  Liebreich  to  the  therapeutic  employment  of  the  drug 
which  he  now  advocates. 
If  a  dose  of  cantharides,  only  just  sufficient  to  cause  acute  poi- 
soning and  death,  be  given  to  a  rabbit,  the  kidney  symptoms  are 
not  such  as  will  account  for  death,  but  the  animal  dies  after  some 
hours  from  dyspnoea.  Post  mortem  the  kidneys  are  not  hyperaemic, 
and  there  is  only  slight  hyperemia  of  the  lungs,  which,  however, 
are  increased  in  consistence,  owing  to  a  slight  exudation,  for  the 
most  part  free  from  cells  and  not  coagulating  spontaneously.  Acute 
lung  oedema  is  not  present.  The  exudation  is  not  preceded  by  a 
change  in  the  blood  pressure  or  in  the  condition  of  the  heart,  and 
seems  to  resemble  that  observed  after  the  application  of  cantharides 
to  the  skin,  in  that  there  is  no  preceding  hyperaemia.  Only  if  large 
doses  be  given  does  an  exudation  containing  cells  take  the  place  of 
a  simple  serous  exudation. 
It  may  be  assumed  that  cantharides  has  a  special  action  on  the 
capillaries,  owing  to  the  peculiar  form  of  irritation  it  causes. 
If  the  vessel  walls  are  not  in  a  normal  condition  they  may  be  more 
susceptible  to  the  irritant  action  of  cantharides,  and  it  seemed  to 
Liebreich  possible  that  in  capillaries  of  decreased  resistant  power, 
such  as  may  be  present  in  diseased  conditions,  those  changes  might 
be  produced  by  very  small  doses  of  cantharides,  which  in  healthy 
tissues  are  only  caused  by  large  doses.  Such  lessened  resistance 
might  occur  through  the  irritation  connected  with  the  presence  of 
bacilli.  Koch's  investigation  into  the  action  of  tuberculin  have 
shown  that  extremely  minute  quantities  of  a  substance  may  cause 
changes  in  irritated  tissues  without  acting  on  the  healthy  tissues. 
Whether  cantharides  could  have  such  an  effect  or  not  seemed 
worthy  of  investigation.  But  for  this  investigation  tincture  of  can- 
tharides would  not  suffice,  since  it  is  not  of  a  uniform  strength,  the 
amount  of  the  chief  active  principle,  cantharidin,  contained  in  can- 
