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THS ADDICTICS LLABILITIES OF SYSTHETIC SUESTITUTES FOR CODSDS

Barris Isbell NI Addiction Research Cantor, P, Lexington, Ey.

R. 7. Fraser, A. wikler, V. a. Hartin and D. E. Rosenberg

o 21-62

To davelop synthstic substitutes for codsine which are lass addietive than codeise.

Pesting for addictiveness vas coapieted or is in progresa on the follouiag nire copounds ring tho reporting year: (1) 1.2'-yároz-2.5.9-tzimethy1-6,7- benzomarphan (1-H-2): (2) 1,2-Hydroxy-5.9-cinsthy1-2(2-phenethy1)-6,7-bencomorphan (I-S-1) given orally; (3) 1-Eydroxyethoxyethy1-4-phenyl-4-propioyl-piperidine (I-D-22); {4) Methotrizeprazine {levomeproeezine, VI-C-5); {5} l-Mirsthylanino-3- phenylindane (X--1); {6) 2-ksino-indane (I-8-2): {7} sixsure of I-H-1 (ses above) and -0-1 (5-allylnorpherazoeine); (8) 21-aydroxy-5,9-dinsthy1-2(3.3-dizethylally1)- 6,7-benzonorphan {11-C-2); (9) 2-yelopropylathy1-2-hydroxr-5.9-dizethy1-6,7- benzeporphan (II-C-3).

of these, I-k-l {orslly) and the mixture of I--l and I-C-1 proved to have addistiveness greater than codeine and have been droppad froa furthor consideration.

I-D-22 (an antitussive) and N-C-2 had leas addictivenesa than ccdeine. I-C-2 deserves further invostigation as an analgesis.

I-E-1, I--2 and vI-C-5 bad no addtctiveness. I-R-1 aud I-z-2 ar prcbably too toxia for eliniozl use. VI-C-5, a chlorprozasine conganer, deterves extensive investization in chronic pain.

M-C-2 has considerabls theorstical interest, since it is zorphine-like behaviorally and ereates rild paysical addiction bus vill not suppress sbstinence frca sorphins.

I7-0-3 is atill deing studied.

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PLANS POR FOTORE

(a) Lons range. Work vill de continued but vill be finished aftor 1 Ootober Ig62 dy the Rational Institutes of Heslth rather than by Ofrice of Eaval Rescaréh.

(b) Isnediate. Drugs to be tested during the coains year includs II-C-> (see above). 14-hydroxy-H-allzi-dihydrocorphine, and such athar cespounds as nre. recosmended by the Comittes on Irug Addiation and Harootics, National Rosearch.. Counail.

CURRENT REPORTS AND FUELICATIONS

: (a) Praser, . P., Essig. C, F., and Holbach, A. B. (ig6i), "Evaluation of carisoprodol and phenyrasidol for addietirsness." Bull. Harcotics, 13, 3-7.

(b) Volbzch, à. B. and Fraser, . . (l962), "Addietion liaoility or thyl-1-[2-cartazethylj-4-phenylpiperidine-4-carboxylate hydrochloride." Bulletin Drug Addiction and Narcotics, National Research Couneil, vashinston, D.a. (bali. , .