title: Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens.
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)(4)OH) 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.
authors.affiliation: Minneapolis Medical Research Foundation, 701 Park Avenue, Minneapolis, Minnesota 55404, USA. prave001@umn.edu
authors.forename: Marco
authors.initials: M
authors.lastname: Pravetoni
authors.forename: Morgan
authors.initials: M
authors.lastname: Le Naour
authors.forename: Ashli M
authors.initials: AM
authors.lastname: Tucker
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Harmon
authors.forename: Tara M
authors.initials: TM
authors.lastname: Hawley
authors.forename: Philip S
authors.initials: PS
authors.lastname: Portoghese
authors.forename: Paul R
authors.initials: PR
authors.lastname: Pentel
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D006241:Haptens; D006853:Hydrocodone / Q000494:pharmacology*; D051379:Mice; D010098:Oxycodone / Q000494:pharmacology*; D051381:Rats; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
chemical_list: D000701:Analgesics, Opioid; D006241:Haptens; D014614:Vaccines, Synthetic; D006853:Hydrocodone; D010098:Oxycodone