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Analgesic and Immunomodulatory Effects of Codeine and Codeine 6-glucuronide

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Abstract

Purpose. The antinociceptive and immunosuppressive effects of codeine and codeine 6-glucuronide were determined in rats after intra-cerebroventricular administration.

Methods. Codeine 6-glucuronide was synthesized using a modification of the Koenigs-Knorr reaction. A lipophilic intermediate formed during synthesis, methyl [codein-6-yl-2,3,4-tri-O-acetyl-β-D-glucopyranosid] uronate, was also tested. Morphine was used as a positive control to compare antinociceptive potencies of these compounds.

Results. All compounds tested produced significant analgesic responses, as assessed by the tail flick model. Additionally, codeine 6-glucuronide showed significantly less immunosuppressive effects than codeine in vitro.

Conclusions. We conclude that codeine 6-glucuronide and related compounds may have clinical benefit in the treatment of pain in immune compromised patients.

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Authors and Affiliations

  1. Department of Pharmaceutics, University of Florida, Gainesville, Florida, 32610

    Vinayak Srinivasan, Donna Wielbo & Ian Tebbett

  2. Department of Pharmacodynamics, University of Florida, Gainesville, Florida, 32610

    James Simpkins

  3. Department of Pharmacy Practice, University of Florida, Gainesville, Florida, 32610

    Janet Karlix

  4. Department of Medicinal Chemistry, University of Florida, Gainesville, Florida, 32610

    Kenneth Sloan

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  1. Vinayak Srinivasan
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  2. Donna Wielbo
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  4. Janet Karlix
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  5. Kenneth Sloan
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  6. Ian Tebbett
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Srinivasan, V., Wielbo, D., Simpkins, J. et al. Analgesic and Immunomodulatory Effects of Codeine and Codeine 6-glucuronide. Pharm Res 13, 296–300 (1996). https://doi.org/10.1023/A:1016059618633

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