a 0 CA. 2 70 0 -.4 0 0 2 -4l 4'rj e4, 0 2 0 -4 2 0 > -4 ri t% (@p (a to to 2 oh Cl. C (% n -1 . 2 .0 2 n 0 -t- 2 =O tr 2 n co vi 2 0 to Ck. 2 cr tn -h CL 0. cr 2 a 2 Lri 0 C* foi 2 to l@D C 2 t-L -'" Z 0 2 CIO 0 2 00 0 2 in 0 2 CL 'O 0 M 0 .10 2 t% OP 44 00 It 2 0 2 ft n 2 64 10 CL zi C",@F n 2 0 -4- cio z 2 co 2 Cof zr O# 2 -C It 2 Ti o co t% 0 2 ot m 2 Zs 4 2e% C4 t* CL r4 2 1) cr u no 0 f;j 2 0 0 - cr CL 2 ;;r V) 0 -4. CIO 2 0 2 of 2 44 46) iA - 2 th 0 et 2 n 2 :71 Cki 0 7 11 requtred: for the eyaluation 'of all new analgesics Uft S-8 are suppi'led by the Department "'f Defense. wort, Accon-nitshed to L)efe Previous work has been Summarized In the annual progress reports sent to Capt. F. H. Quimby and Capt. T. K. Ru 2 ebush Of the Physiology Branch# Office of Naval Res ear ch .,T-z'o drugs have been developed which are promising potenttal 3ubIstitutes for codtifte for relief of cough, These drugs are 11) dextromethorphan, and t2) nareoffne'. Neither drug possesses anY addle flofv llability anct both have r,tiati,vely totj foxi city. The studies reported of @he meeting of Comnttfee-on Drtv$; Addictlo.-i and Narcotics Of the National Retcarch Ctunc!i, t,-i -,'ta2nuall'y lgS7, continue to Indicate that the drugs are ag effective as co-Jetne for relief Of Cough. r seens almost certain* therefore$ that the anftfussive phase of the problem hasg In a gense, been solved. Although the anfifustive problem Is no toneer as pres3lng 'i'iere are still 2 uG s .r no c n mm I ;cj#i are kirown to be as efftc@tive aid saize as todelne for rellef of ,-..Ild gred-,s of patio '.'ore f.han 35 rAa.Lzrials havz now beci :crecr,.-d for f@ts at!r,-Ioa*zo The outstantling substancec ivhtch ha* been develooed Is A-alpha-4-dlr@-iefhvlamino-1,41-dtphenvi- 3-r-ethyl-4-pr'oplo,,ioxybutan-,, or d-Propoxyphznz. but unconfirmed work lndtcdfes that th Is compound is as effective as codeine a,& an analgesic In clinical practi,ea@.. Extonslve work'has shoin thatp although the compound possesses addictive potentialities., the overall addiction liability Is cons2iderably lcss'than that of codeine. This drugj, therefore,, Is quite promtsinst but final evaluation FnUSt Wait CoMpl etlon of extensive clinical trial for relief of Palo. 3. Need for C6nflnuafflon of the Project T@2.c.chief need for continuation of the project Is related to uhcertatntv concerning the aftaigesic potency of d-Pro. poxyphence If clinical trials show that- this d,-ug ts &s effective as codeine then all aspects of our original -roblc;n would be completely solved. Since., howeverv we cannot 2bz ccrfal,,t of this time that d-?ropoiyphenz will replace codzine In clinic@al use, it 1:;-stlit essential-l-bat the search for ty-tifhetic substitute$ must be continued since the larger f,@e nunber of ccmpcunds tested the greafer the chance of finelig completely adequaft substitutes. 4. 7.'ork Prooosed During t,%,z period from I Jul-,i 19c@'7 ic 3'v June pro p6;e to fesf fhe addictive propcrflc3 of phenifhyl r.-orphtnan, D-3-hydroxy-.N-phzncfhyl i-norphinan, .N8Larr--:)rphiney '@arcaLleitie., and N-ailyldil,.Ydrohydrox.1,@ codeino,-ic. 164 I ri addition., studies Of other substances refert- ed by the CO-mm@l'ff cc on Drug Addict Ion and Narcot fc-s' of 'the Nat long I Research Council will be carried on. -Y-ethods The methods to be used are the sta2ndard addiction liability testing methods of f.he Nlh",-iAddiction Research Ce.,ifer. These methods are accepted as'standard by the Committee on'Drug Addiction ancl Narcotics and have been descrtbzd In previous project descriptions,. which shoutd be consuffed T'or details. 6. Evaluation of Dafa T,2he evaluation of data obfainee In the- addlcflon itab.lilfy progran. has also been discussed In previOUS PrOjeC@ 4dC3cripf:ons. 7. Lora t Ion of ilro jec t 'Work will be carried out at the Nlhl+ Addiction Research Cen@,zrp -*HS Hospital, Lexingtoni Kentucky. This Insfi'fuflon provides fhe two necessary facillfie-@ for he type of viork to ue uftd@-riaken-0 i i ) a o o, o I o fi t *o;vnteer for experiments with drugs-, and (2) sfrlcf envlronmen-fat control w,) lcS. prevent& fhe lnalro,48ucf ion o-ft' druis othcr f!ian fho3z u,-i c.?rs f un t'Fl e xr n,. e ns I u a to n 8. Exper lmental Personnel @.',brk will bc carried out under fhe;di@recfton of Ha-rr-ts r. trccf or., Ni@@-@H Addict ton Rese4r'ch Center. TI) Is- Invest loafer has had thirteen Years of experience In research In' narcotic drug addiction and has published many papers In f-he field. H-c will be 'assisted bY two other -zocrienc-d physi Dr- H. F. Fra2ser and Dr. Abraham %Yltkler., both of iqhom havi;-. In research'In addiction, with rlany had extensive experlznce pubtf--ations. In addition to these r-ledical personnel the part-time services of a btochzmts'4- and reszarch psycholo-I.-,f will be made available. A special ward T'or fh4;@ conduct of fbesc studies Is currently In operation* 9. 4c- f c dCost The am-ounf of money requesfed has bz--n &eld/fhg 3aMZ figure as %7a savailable In f 1-.ca I yesr 1957. ?ersonnel 6 2Ps.ychlafrtc Aid@.-s OS-5 ($4145.@ pea*) Ph ys Ica I '@'c leice -A lde GS-5 2. -Pescrvz @for Pr on, I u,.i Pa y 11-1[Ght differentials !Iolic!--.yl 0,.,erfime) 3 Tray.-*' 4. K40,@iscel laneous E-pense --@w 70ta I----------- 14 is 'cc 1 1 D c o r 2 ?o-7 r L, z r