Ltj t..t ::) 4. 'Ti 2 *i _iz C LLS 2 ti qy CL 2 V EJ) z 15i W 2 uj 0 44 C C: -V W ui 0 0 2 v 'U W W 0 t-I CL U, U 2 x IT) 0 > I-- 2 0 tn a C$ r. C C)4 C: 2 C t.- CN t. W ri en do 2 16. @Ic 3F 2 ti fw r_ OU -Ir- 2 -9-- 0 2 30 ct 2 0 eV v v o 2 OL :@l to Z' - 5 -U tp C (Z 0 U VD r k A c c,@,-, -n h d f c Annual ?roc,-ress Reiort 3ent This Is sururarized in th to Ori F. H. t:",^uinbyj,, @-"zad of the p2hy3loloGy Branch, Office of In lanuiry 1954. Ptscarch, The nost prc,.,nisin@- drug yet d-velopcd In the procra.,i Is the dc'xtrorotatory 3-methyleth2er of Nl-.n-,thylmorphinan. This co-,npound Is completely deveid of addictitn liablit@v-@,and Is of suf'ficiently low toxicity to be safc for hu:nan USC* In experimental 211 has considerable an t i tt-s3 'tve act;l-., I f-t and trial for antitusslyz activity, u@ndci- ;,P- t4ca-. I con d I t I o n s Is now underway. The rcsuits bbtaiocd with this druc- as a 2 c I In i-@a I 4nt if us s I ve ar-e s t III con f II ci in- a od it is nit yet cc r t a I n whc t h t r I t vou I d be a n *de qua t t s u%l@- -. t I t u t c f r c --c L, iii -c for this purpose. I t I s a I s a nc -ii,.i a t t!li 2'if u I s coi-n,@p I q t c I V Ineffective as an on4locsIc and viould iof serve as a substitute@ for cadeing for this puroo.-c. a.-id I 2-2-d 1 ph tn-,, I din I n--@c t h-f I v a I 2c r a t c z dye tv o n. I 'I a 4 r c ?r li @.-4o code lre. @rel'iti;n4ry c I I n i c a t t I a I c, t i s cl r u s i,-.i I I a rto t@ic-sc of t),,c vi)lcr.3ics c@lzscribe,-' In -7 ir cc,! f C!:@ C r kAccf.@-n: r Tli s, Is sum,-.1.3r!zcu th;z Arnual to I)r. F. H..@-ut.-nbf f,%c i,hy3tol ry aranch ffice of N-aval Rescarcht2 in janudry 1954. The most pro-iii.ir.,: druo yet 4evelopid In the prr,-cra-.q Is the dex@roretatory 3-;nethyle4ther of 'rhis co.,li-,ound -omp-l@;tciy devoid of addiction llobtltty -and Is of su,"ficiently low toxicity fo be 34te for hu:7-an cxpertmental ailir@41& It hds -Antitu3sive activity and trial f-,)r 4.-Ititu3slv-- actlvity under clinical coftditlons 2 Is now undtrway. The results obtalne@3 with th Is druc os a I.-.Iintcal zntitussivv are 3fill --onfilctins and if ts not yct cerfdln whether It '--z an su'@,,stliute for f2OC fhl3 pur;)Oseo it. Is d"so -.nl3wn t@at $'.he drv- Is llneft'ec%kive as an andizesic and W-.Vld tot SCrVe a3 4- for codtins f .r LI n,@ 2 valeratzs have y codzi.ne. Prel I -,i I it ry c I It i ca It r I a I s w I t hi hs c e. r@,s v c !@een c c dC I.: I bed s t2'le v-sicrai'cz -a r -3,-: r a p'l a.-. d mz-@ @trv@@ Zs O I u op4n41 I Cq As a pp uq Su I PU! j z c- C- AZ 2 ti 4 a q I I I 3 J A 4 AC2; .1 C;@ 4 4 u @uA 41 P:u'P 'leij4 ILziullD ul el Gs as-ltt'4 10 tuo P.1 0.1 e- :t 1,21 t 'L - - - & jaaal it C, Li s I El 4 ut' 4 od 3A z 4 4 P q 4 0.1 4 r,,.; i 4 u c- 2 I P pu 0 aAl Isn4t4u@, uc- t-L, Auet--,j-,3 2 3sn U I S Ocf L-@,:) 1-t zoio mot P 10 A u 0 4 :)I p p P P .0. P q A u,? j 9 0 j u -P 2 x@4 -Zu nt'! 4UO3 1 1 4 s q4 qt 'bulDPOZ 04 Jei!wls SA.,,-P DISZBIVUP pllw r zq Aiqpqojd IIIA' 41- 4P244 ut UPJOU.,OjC! lAq4auj-p@iZA0 ase4u;,App auo 2 0 41 -zulzpo* JOVL :@4m4i4zqns -IIP14u340d@.1? so pzj23plsuo.* -Iq 4431W punac!iuO-7 z@44 u P.$ C#woin Jo JD4421 '442u.-P 8q4. 4414 sigIJ4 -IPDIL'! 1* 0 vwo-wtno aqi u O Su I 1)u:lda.,,2@l au I qdtou; $0. 4EI44 UP44 CIS31 -tri $I 4rPue4 J3440 z@4 UO 4PuP 3ulOP03 10 4vq4 -UP44 J-14P3JB 4L*4xtaw0c Aiqvqojd sl 2 A41liqr!l U014:)IPPP 1;41 *,*ul4c!Jout wojj zouzut4sqp sassaljcd-nt /,IIP14JPd Puc 3111-aulqciiotu PIILU sgq Snip si44..JO,tL';JOI Ai--4P40JOADI 2141 0441tiqo,ll uollzlppp 10 ploaap Pup Uew ut @4.iz4f At24:tfd"woD ti upul4djou,-AxojpAq-lAy4aLuip-N Z-(3 IV* Proiz).,.@sed 1954 to July 1955 we Durtno the period July conplete thg work on the Isomers of 2,,N-dinefhytrnor@.>hinan and on 4.4-diphenyl-.,t@-dimet@yt4.,nin2o-hcxanone-3. In addition to this we hooe to 4za.-nine the potentialities of the myristti estcr of rnorphine and of 3-hydroxy-N-.:n--thylmorphinan4 Two new approaches to the problem will be'explorcd. s of at2tc,.npts to attenuat "th One of thcsc consist c c poten%-Y --*ad a8diction tia@hillily ofl,the synthetic drugs meth4dont and Dromoran by mixing the-,.I with specific antanonirts,, 2 morphine and N-allyinardr--,I-.ioran,, a,rd- suc-h- O+hcr anf4goillits as may be rccl-,mnendcd b-y the O.ruq r'lld(itc-tioiv t'ae N"ational Research Council. In this co.-.nectton it m,-jy 2bA- necezsary to stiu---4'y ib-z c)ropertics o't' a nu.;4@ber of r,.-w in the hope of findirtc- an h*ch are or3'ly efitctivc. ihe followtnrj antaconists will be exarnlnqd,- (1)4 2 t2) iN-Prqpyi-dihydroporniorphttie, 13Y a t r y and r n c rr c.,no rn *-,id t6) the s pp I y f i i-, bi co. blockInS a g e n3 b c f a - d- ih o 4 ti 't r oy c a s ell C .3 ell t- 0 2 rA 40 16I 2 W %h CIZ CIL S. 0 2 - 04 C: ti 2 > t4) 40 v tf) 2 . C 0 64 OL 4- Vb 40 d3 2 0 W > L) 4i ri W 2 .0 a .0 do 0 W a v 2 A3 4- 0 C, r 4D k) 2 44 C- > 0 t3 it 4. 0 W W 0 2 40 v to t) v %AJ VI 2 V- 06 C C! -Ok. W W 6 Lt. cx n. v I I I Exoertm-ental Personnel The -g 11 'W-e carrs',ed ou! under the direction of Director of Research Nlt.,H-Addiction Harris Is be I I tA.D. Research Center. This InVC3tigator has had ten years of exoerl- encc In research In norcotic druv, addiction and has publistied many paners to the field. He wil I bC ass is fCCf -by two other experienced physictans., Dr. H. F. Fraser and Dr. Abrob4m-'Vlkler# both of whom have,h4d.extensi.ve experience2 In research In addoidtion. In addition to thc.se med4tcal personnel, the part. time services of a Slochen-ist and Research Psychologist will bit made- ava I la b le. 'A s' ec la I wa rd for'corid'udf tng the. s f ud les p Is 2currently In operation. llx . Estimated @"Ost Pe rs'on ne I 6' Psychiatric Aide, GS--S @w I Phy3ical Science Aide, GS-4 I Physiologist C-S-7 2. Reserve for night 'holiday a'nd overtio-c pay t@-tilocel laneous expenses Total lte'm 3 miscglianeou; expensest, licludes m. n c''fo.- the pu r c ba!s cof dru@;s, chei@- Ica I sc,, I a s s -.va r celectr2oencephalcer,*P@SIC. .and photographic paper oeed I es, Sy-rin!ge.s- etc* 71 il Ha.rr!s I 1 1 Director o' N'escarch T 8 rn