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Pharmacological Implications of the Conformation of the Methadone Base

Abstract

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.

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BÜRGI, H., DUNITZ, J. & SHEFTER, E. Pharmacological Implications of the Conformation of the Methadone Base. Nature New Biology 244, 186–188 (1973). https://doi.org/10.1038/newbio244186b0

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