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On checking I find that I have only 50 mg. of the drug MK-57. Chemically this compound is 6-methyl-△-6-desoxymorphine. I am writing Merck and Company to see if I can obtain an additional supply.

Megimide is\_being shipped under separate cover.

I am enclosing three reprints on suggestibility by V. H. Vogel.

I am also enclosing tables of the preliminary tabulations on C-9 and MX. These experiments were preceded by preliminary titration in which' it was determined that 0.6 to l.0 mg. of M for each 70 kilogramsof bodyweight induced definite cardiovascular changes. Thereafter, a comparison was carried out in 15/subjects, using the randomized Latin Square design. The drugs tested were placebo; 0.6 mg MX (per 70 kilos); 1 mg MX (per 70 kilos); and 1 mg. C-9 (per 70 kilos). Measurements including reclining pulse rate (after 10 minutes in bed); standing pulse rate (counted for one minute after standing for one minute);,and number of positive responses to a simple system check-list based on our earlier work with C-9.

Two tables are enclosed. One shows the time course of the effect with different drugs. In this table it is evident that the effect does not begin until the second hour and persists at least until the twelfth hour.

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C-760

eparfm. of HEALTH, EDUCATION, AND LFAr , Public Health Service NATIONAL INSTITUTES OF HEALTH 23 October 1956

IN REPLYING AGORESS THE NATIONAL INSTITUTE OF MENTAL HEALTH ABBICTION RESEAACH CENTER U.S. PUBUC HtALTH SERYICE HOSMTAL P. O. B0x 2000 LEIINGTON. KENTUCRY

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The second table shows the average changes with the four different combinations. You will notice that there is a distinct difference between both doses of MX and placebo, as well as between C-9 and placebo. There is also a definite dose response between the 0.6- and 1.0-mg. level with MX. There may be a tendency for cardiovascular effects of C-9 to be more pronounced in the overall course. I.cannot be certain of this until the statistical analysis has been completed. When this is accomplished I will send you another report and will also work up table showing the details on the cardiovascular measurements made in the older work with C-9.

.Sincerely yours,

二Harris Isbell, M.D.Director

HI:rn

Enclosures: 5

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Ropresents sum of rates obtained at one.to nine hours after drug.

2 Counted for one minute after standing one minute. Represents average sum of rates obtained at one to nine hours after drug.

Represznts total of positive responszs In 23 hours.

x Dose In ng. for zach 70 kg. of body welght.

AVERAGE CHANGES ↓ STANDARD ERRORS AFTER-C-9 AND MX IN 15 SUS JECTS

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