Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens

Marco Pravetoni, Morgan Le Naour, Ashli M. Tucker, Theresa M. Harmon, Tara M. Hawley, Philip S. Portoghese, Paul R. Pentel

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Prescription opioids abuse and associated deaths are an emerging concern in the USA. Vaccination against prescription opioids may provide an alternative to pharmacotherapy. An oxycodone hapten containing a tetraglycine linker at the C6 position (6OXY(Gly)4OH) conjugated to keyhole limpet hemocyanin (KLH) has shown early proof-of-efficacy in rodents as a candidate immunogen (6OXY(Gly)4-KLH) for the treatment of oxycodone abuse. In this study, oxycodone-based and hydrocodone-based haptens were conjugated to KLH to generate immunogens that would recognize both oxycodone and hydrocodone. Vaccination with 6OXY(Gly)4-KLH increased drug binding in serum, reduced drug distribution to brain, and blunted analgesia for both oxycodone and hydrocodone. An analogous C6-linked hydrocodone vaccine blocked hydrocodone effects but less so than 6OXY(Gly)4-KLH. C8-Linked hydrocodone immunogens had only limited efficacy. Amide conjugation showed higher haptenation ratios and greater efficacy than thioether conjugation to maleimide activated KLH (mKLH). The 6OXY(Gly)4-KLH vaccine may be used for treatment of prescription opioid abuse.

Original languageEnglish (US)
Pages (from-to)915-923
Number of pages9
JournalJournal of Medicinal Chemistry
Volume56
Issue number3
DOIs
StatePublished - Feb 14 2013

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glycyl-glycyl-glycyl-glycine
Hydrocodone
Oxycodone
Haptens
Opioid Analgesics
Vaccination
Prescriptions
Vaccines
Sulfides
keyhole-limpet hemocyanin
Amides
Pharmaceutical Preparations
Analgesia
Rodentia
Drug Therapy

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Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens. / Pravetoni, Marco; Le Naour, Morgan; Tucker, Ashli M.; Harmon, Theresa M.; Hawley, Tara M.; Portoghese, Philip S.; Pentel, Paul R.

In: Journal of Medicinal Chemistry, Vol. 56, No. 3, 14.02.2013, p. 915-923.

Research output: Contribution to journalArticle

Pravetoni, Marco ; Le Naour, Morgan ; Tucker, Ashli M. ; Harmon, Theresa M. ; Hawley, Tara M. ; Portoghese, Philip S. ; Pentel, Paul R. / Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 3. pp. 915-923.
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