Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Pharmacological Implications of the Conformation of the Methadone Base


METHADONE (6-dimethylamino-4,4-diphenyl-3-heptanone) is unusual among the potent narcotic analgesics in that it possesses a high degree of conformational flexibility. It has been proposed that the protonated and unprotonated- forms of this molecule occur preferentially in cyclic conformations1,2, but a crystallographic study3 of S(+)-methadone hydrobromide revealed that the protonated form of the molecule, at least in the solid state, prefers an extended (acyclic) conformation. Here we report the conformation of the methadone base observed in crystalline material and its biological implications.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. Beckett, A. H., J. Pharm. Pharmac., 8, 848 (1956).

    Article  CAS  Google Scholar 

  2. Portoghese, P. S., and Williams, D. A., J. Med. Chem., 12, 839 (1969).

    Article  CAS  Google Scholar 

  3. Hanson, A. W., and Ahmed, F. R., Acta Cryst., 11, 724 (1958).

    Article  CAS  Google Scholar 

  4. Germain, G., Main, P., and Woolfson, M. M., Acta Cryst., B26, 274 (1970).

    Article  CAS  Google Scholar 

  5. Germain, G., Main, P., and Woolfson, M. M., Acta Cryst., A27, 368 (1971).

    Article  CAS  Google Scholar 

  6. Leonard, N. J., Rec. Chem. Progr., 17, 243 (1956).

    CAS  Google Scholar 

  7. Leonard, N. J., Morrow, D. F., and Rogers, M. T., J. Amer. Chem. Soc., 79, 5476 (1959).

    Article  Google Scholar 

  8. Leonard, N. J., Oki, M., and Chiavarelli, S., J. Amer. Chem. Soc., 77, 6234 (1955).

    Article  CAS  Google Scholar 

  9. Anet, F. A., Bailey, A. S., and Robinson, R., Chemistry and Industry, 944 (1953).

  10. Hall, S. R., and Ahmed, F. R., Acta Cryst., B24, 346 (1968).

    Article  CAS  Google Scholar 

  11. Hall, S. R., and Ahmed, F. R., Acta Cryst., B24, 337 (1968).

    Article  CAS  Google Scholar 

  12. Birnbaum, K. B., Acta Cryst., B28, 2825 (1972).

    Article  CAS  Google Scholar 

  13. Oldendorf, W. H., Hyman, S., Braun, L., and Oldendorf, S. Z., Science N.Y., 178, 984 (1972).

    Article  CAS  Google Scholar 

  14. Handbook of Biochemistry (edit. by Sober, H. A.), 206 (The Chemical Rubber Co., Cleveland, Ohio, USA, 1970).

  15. Jacob, E. J., Thompson, H. B., and Bartell, L. S., J. Chem. Phys., 47, 3748 (1967).

    Article  Google Scholar 

  16. von Cube, B., Teschemacher, H., Herz, A., and Hess, R., Naunyn-Schmiedebergs Arch. Pharmak., 265, 455 (1970).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Cite this article

BÜRGI, H., DUNITZ, J. & SHEFTER, E. Pharmacological Implications of the Conformation of the Methadone Base. Nature New Biology 244, 186–188 (1973).

Download citation

  • Received:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing