Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners

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Abstract

A series of 3-O-acyl-6-O-sulfate esters of morphine, dihydromorphine, N-methylmorphinium iodide, codeine, and dihydrocodeine were prepared and evaluated for their ability to bind to μ-, δ-, κ1-, κ2-, and κ3-opiate receptors. Several compounds exhibited good affinity for the μ-opiate receptor. Morphine-3-O-propionyl-6-O-sulfate had four times greater affinity than morphine at the μ-opiate receptor and was the most selective compound at this receptor subtype.

Graphical abstract

A series of 3-O-acyl-6-O-sulfate esters of morphine, dihydromorphine, N-methylmorphinium iodide, codeine, and dihydrocodeine were prepared and evaluated for their ability to bind to μ-, δ-, κ1-, κ2-, and κ3-opiate receptors. Several compounds exhibited good affinity for the μ-opiate receptor. Morphine-3-O-propionyl-6-O-sulfate had four times greater affinity than morphine at the μ-opiate receptor and was the most selective compound at this receptor subtype.

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Acknowledgment

This research was supported by a Grant from National Institute on Drug Abuse (Medications Development Division Contract No. 271-89-8159).

References and notes (21)

  • M. Mori et al.

    Life Sci.

    (1972)
  • S.Y. Yeh et al.

    J. Pharm. Sci.

    (1971)
  • E. Nagano et al.

    Life Sciences

    (2000)
  • C.E. Brown et al.

    J. Pharm. Sci.

    (1985)
  • K. Oguri et al.

    Life Sci.

    (1987)
  • A. Zuckerman et al.

    Brain Res.

    (1999)
  • A.A. Houdi et al.

    Pharmacol., Biochem. Behav.

    (1996)
  • D. Preechagoon et al.

    Int. J. Pharm.

    (1998)
  • J. Fridrichsons et al.

    Tetrahedron Lett.

    (1968)
  • P. Sjoegren et al.

    Pol. Med. Paliatywna

    (2004)
There are more references available in the full text version of this article.

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