26  Action  of  Morphine  and  Derivatives.  { 
Am.  Jour.  Pharrn. 
Jau.,  1891. 
morphine  first  depresses  and  then  stimulates  the  cord,  but  the 
experiments  of  Stockman  and  Dott  lead  them  to  the  conclusion 
that  this  view  is  erroneous.  Morphine  they  hold  in  small  doses 
depresses  the  action  of  the  cord  ;  in  larger  doses  stimulates  it.  The 
late  appearance  of  increased  reflexes  is  they  think  due  to  the  fact 
that  at  first  only  a  small  quantity  of  morphine  reaches  the  cord.  It 
has  been  held  by  some  observers  that  morphine  is  capable  of  directly 
paralyzing  the  motor  endings  of  nerves,  but  Witkowski  considered 
that  the  depressed  excitability  of  the  motor  endings  was  the  result 
of  the  exhaustion  consequent  on  the  prolonged  tetanus  caused  by 
morphine.  Stockman  and  Dott  record  experiments  tending  to  show 
that  morphine  does  paralyze  more  or  less  completely  the  nerve  end- 
ings, but  only  when  large  amounts  come  into  contact  with  them. 
The  end  organs,  however,  are  certainly  not  very  sensitive  to  the 
action  of  morphine.  With  sensory  nerves  the  state  of  affairs  seems 
to  be  much  the  same.  Mammals  are  affected  by  morphine  like 
frogs,  but  die  so  soon  from  paralysis  of  the  respiratory  centre  that  the 
tetanic  stage  is  not  usually  well  developed.  In  man  tetanic  symp- 
toms are  very  exceptional,  for  after  therapeutic  doses  the  amount 
of  morphine  reaching  the  peripheral  nerve  endings  is  not  usually 
sufficient  to  affect  them. 
After  thus  setting  forth  the  physiological  action  of  morphine,  the 
authors  proceed  to  compare  with  it  the  influence  of  groups  of  new 
compounds  which  they  prepared  from  morphine  by  substitution  and 
addition. 
Substitution  of  alkyls. — Three  compounds  were  produced  by  the 
replacement  of  an  atom  of  hydrogen  in  morphine  by  an  atom  of 
methyl,  ethyl,  and  amyl,  respectively,  viz : 
Methyl  morphine,  C1 7U1 8N02OCH3 
Ethyl  morphine,  C1  vH18N02OC2H5 
Amyl  morphine,   CiyHigNOaOCgHn 
Chemically  these  substances  may  be  looked  upon  as  the  methyl, 
ethyl,  and  amyl  ethers  of  morphine.  The  first  of  the  three  is  the 
well-known  alkaloid  codeine.  Comparing  the  physiological  effects 
of  these  three  substances  with  that  of  morphine,  it  was  found  that 
in  all  the  narcotic  action  was  much  diminished  by  the  substitution 
of  the  alkyl  radicle  for  the  hydrogen  atom,  whilst  the  tetanic  action 
and  the  action  on  the  motor  nerves  was  increased.  The  paralyzing 
action,  too,  on  the  motor  nerve  endings  was  more  decided.  The 
