September 23,  1950'
                                   Harris Isbell,  ?,I.D.,  Director
                                   Addiction Research Center
                                   National Institutes of Nlental Health
                                   U.S.  Public i-iealch Ser@,,ice Hospilt-lal
                   2                Box 2000
                                   Lexington,  Kentucky
                                   Dear      Dr.     Isbell:
                                              The     information. which I promised you is as follovlrs:
                                              Toxicity:   In the           -.notise,    by    I.    P.    roule,     t'.-i-     LD
                                                                      2                                                  -        5,)          
mg     g.
                                   In the     dog,           I.V.  roul.-e,  it i--@ 100                              The                      
trarouil-.Z-
                                   ing dose for the do,7 by-the 1. V,.  routa, is                             O@o, n,.z-11
                2                                                                                                                   Tiie   
co@--,.Dou-,Id
                                   someti=.es prodices'mic.-:,is,  bt-.@. often one can                                ol)se.-ve
riydri---,s@.s.
                                   '.In     the     barbiltaiizzd     dog,     1-@,raGydard-.a     is      produced      at      a          o@
0. 1 r.-
                                   I.V.   T,ii.s resronsei'z nol.- bi-                  cli-.-'ed by 07io,,- al*ropir.;.zation or
                                   This b.--adycirdia is a'As,,) p.-c-rn.i-.ient in the ir,6-act,  u-tanestiletized a,-il,-,al
                                   even at a lo-,ver dose.   Hypotherr,,nia is prominent folio-.wincf I
                                   I. V.,  in @h.- docr.   The body temperature L'.@llls 4 to 'I  degrees C.
                                   24 hours and gradually retur,-is 'lo nor=...-at over -a several day
                        2           At    ti-l,-    dose    level    of    100    rr.-r/k-    s,--vere     diart,hca     is     prczluced    
L-1     'ke
                                   dog.    f lie ni.ctitati.-I,,--l -nerrbrane              of    the    do,--    has    a    pure             
in-
                                                                                 2                   4 -1 L
                                             t;        -d                     rc."azcc,      '-.ti "-s                           wo
                                                 n ".. 1   4        -@.L                                                L  J.        UA."   -e.
Et:;     i.,I-
                                                       it z,--duc3s ti-4-- ro!-               cen-@i-al                            outfla,,,
s'nc-2-       t  a
                                                                     it a charactoristic                           r::,,ic b'-       'na       
'o
                                   drug does not e-.<hib,                                              adrene      2          soc--            
, L .4
                                                                                                                                  .-,J.  -,
act-  -    a:-d
                                   g,nn--!-;.on-.c bloc'@--.de -as un',i',e.e ly.            At7.           all drii7s in @4..bis s-2r;,i@s, 2
ataxia
                                   L-, a                      -zin,-n in t'tia dr,.,-...               t'.
                                   Aa -- -,ins ;o a!,--@-t--ar at     a!':. o u t I,- -- rri 44,n 1,@.- u -..n                   i4ose
                                   a,--ed -v7i-t'i i-espi.-atory de,,-;ress4.c;.i.   B.,iLli of t,.iese- t-i.-c.,cts occur at                  
d. os  e
                                   levels belo-.v tnat recuired to pro-duce bradycardia.

                                                         2
                                                                                        drama-
                            The  co     on carotid occlusion pressor response is
                      tically reduced  in the barbitalized c!og -within 30 minutes after the
                                                    -is material.  The pressor respor;se eli-
                      injectlon of s.-2nall c!oses of t@t.
                      cited by. central vagal stiri,.ulation may be F            ced or e%,en re-
                                                                   ._,reatly redl
                      versed by small doses of ti-ie material.  This drug ap-larently r,--duces
                      the perip,ieral vascular resistance.  This is manifested by c'ecrease
                      in m,,2nimum arterial  blood  pressure.  A  given  dose  o)'  epinephrine
                      at this point will produce a greater pressor response than it would.
                      bi-fore the drug was administered.  The increased vascular response
                      to epinephrine occurs in dogs with doses around 0. 05 m. -g/'&%-g.  I.-ihibi-
                      tion of t'll-2 C.C.O. pressor response l2ikewise  occur5  at  this  dose.
                      The dog's blood pressu're is reduced about 30','@o by a dose of 0. I r-g/kg.
                            It seems strange to me that this   material is not more antarlonis-
                      tic to LSD-25-'than v.,as indicated in the trials of the two given simul-
                      taneouslly. For this reason -il2one it 1.7ould see:.n useful to study the
                      dru-y further.
                            I'M loaing forward    to taA'L%-ing to you on the 17t,ri.
                                                                    Sincerelv yours,
                                           2  S p,. e?,-@r. b e- r I D,@,j
                                                 4                Peclassifred  by   -18741'5-,
                                                                 'date