rN of HEALTH, EDUCATION, AND -LFA! Public NATIONAL I NSTITUTES OF H E-A LT H 23 October 1956 lit RUPLYING A00RES3 THC MATIO14AL IFt.;;;;7 , A4 tMrAt. H ZALTH AGGicTion RXSCARCH C2CXTIR U.S. PUBUC HEALrm 54Rvict HospiTAL P. 0. 130" 2000 LIXINGTON. KINTUCKY -7 On checking I find that I have onl.y 50 mg. of the drug W-57. Chemically this compound is 6-methyl-4,-6-desoxymorphine. I air. writing@il-ferck and Company to see if I can obtain aL-1. additional supply. Megimide is-being shipped under sedaratt cover. I -am enclbsi ng 'hree'repri, L. 4ts on suggestibility by V. H. Vogel. I am'also enclosin@ tables of the preliminary tabulations on C-9 and @,'X. Thes'e experiment2s were preceded by preli.,iiinary titration in whtch'it was determined that 0.6 to 1.0 mg. of f or each 7b kilograms-.-of bodywei ht induced 9 cardiovascular changes. Thereafter, a comparison was carried out in 15"subjects, using the randomized Latin Square design. The drugs tested were placebo; 0.6 mg2 Aa (per 70 kilos); I mg ?AX (per 70 kilos); and I mg. C-9 (per 70 kilos). %Ieasure- ments including reclining pulse rate (af4'.er 10 minutes in bed); standing pulse rate (counted for one minute after standing for one minute); and numbe@- of positive responses to a simple system check-list based on our earlier work wi4.-h C-9. 4 Two tables are enclosed. One shows the time course of the 'L f f e effect with d- -rent drugs. In this table.it is evident that t,ie effect does not be.ain ul-,til the s-econd hour and persists at least until the twelfth hour. Page 2 The second table shows the alerage changes with the four different combinations. You will notice that there is a distinct difference between both doses of @,@X and placebo, as well as between C-9 and placebo. There is also a definite dose response between the O.'O- and 1.0-mg. level with ,.4X. There may be a *,.endency for cardiovascular effects of C-9 to be more pronounced in the overall course. I cannot be certain of this until the st'.atist;.cal analysis has been comp,eted. 1,Vhen this is accomdlished I will send you another'reloort and wi,ll also work up table showing the details on the ca9rdiovascular measurements made in the older work with C-9. Sincerely yours, Harris Isbell, ?".D. D i r e c to r HI:rn F-nclosur,es: TI.@,IE COURSN@ OF C-Q EFcr-CT') s Ul. DRUG HOUR BEFORE C)P, AF TEt) 1) c- I.,r, @2 3 4 2 @5 4.7 @8 @Q 411 r P I a c e bo 6 1 66 64 63 6@ 67 7 0 6 5 66 64 7 1 .07 .1 610 6 1 65 66 67 66 70 7? 69 67 68 7 '7 3 hix 02.6 SE l@ilx I .0 6 OL 66 70 7 2 6Q 74 7 7 3 7 ? 72 6 1 C-9 I o 6 1 66 75 73 (i 9 7 1 7 9 7,4 74 2 7 4 7 7 7 p 1, a c e b o 90 8 5 .91 8 9 P 5 F9 q3'' @-9 91 R,,, p (71 f! 0') V) f-@ SE @ND I t@@ix 0.6 86- 93 OF Q3. 97 2 1 ol/) I Co. Q7 1 97 9 5 P 7 I? en 8 5 tv.. x I .0 9(' 8 8 I C6 I C,7. I I I 0 1 I C?6 (,@7 1 ITE C-9 1 2.0 '00 11.2 113 1 14 f OS I C, 97 C9- I I 0 1 1 1 107 P I a cc bo 0 0 1 1 0.(5 20 0 2 2 3 3 4 4 3 "2 S T I x 1.0 0 0 9- 3 4 5 5 5 5 5 3 1 0 0 2 3 4 "4 6 5 2 s 14 Doses expressed as' mg/70 k .9 (e.g. 1*0 1,0 irg for %e,3ch 70 Pg b o,-] V we gilt 1. 1--ounfed for I Oinute after standing quietly 4 for I minufe. AVERAGC S TA., ND,,k R D E R R OR S Ar- I'ER C - 9 A I,[) NiX I N I 5 5 U,"@ 5 ,%@'.E A S U,"%J -t P LAC c. '--'O &IX t@. x C-9 2 0.6 1.0 1.0 RE'-@L ILN I @C- p ULSE RA TE 590 4 1 2 611 4 I 1 6 4 4 16 65 4 4 22 S T,,@ PID ING P U L 5 -RATE 804 4. 16 859. 4. e)o 927 4 13 945 4 31 3 4 1 "-iU'c' S T lct4s 13' 4. 7 46 4. 1 8 45 4 10 D,pre@,?n@s su-r. of rates obt@tned a-.f one.fo ninc hours aff-,.r drva. 2 Counted for one minule aft,:r standing one rmlnvfe. Rz,-.resents average sum of-!rates obtained at one to nine hour.- af5ter -@lrug. Represzifs total of posItTye re.-.ponszs In '2.@, bovrs. Dose for zec@ k;. of f)o-.Iy