Behavioral effects of benzylideneoxymorphone (BOM), a low efficacy µ opioid receptor agonist and a δ opioid receptor antagonist

Psychopharmacology (Berl). 2020 Dec;237(12):3591-3602. doi: 10.1007/s00213-020-05638-1. Epub 2020 Aug 21.

Abstract

Rationale: Opioids remain the drugs of choice for treating moderate to severe pain, although adverse effects often limit use. Drugs acting concomitantly as agonists at μ opioid receptors and antagonists at δ opioid receptors produce antinociceptive effects with a reduced profile of adverse effects; one such drug, benzylideneoxymorphone (BOM), might further limit adverse effects because it appears to have lower pharmacological efficacy than other μ opioid receptor agonists.

Objectives: The current study compared the acute behavioral effects of BOM with the effects of other μ opioid receptor agonists.

Methods: Discriminative stimulus and rate-decreasing effects were studied in 1 group of 7 rats discriminating 3.2 mg/kg morphine while responding under a fixed-ratio 10 schedule of food presentation. Antinociceptive effects were determined in a second group of 8 rats using a warm water tail withdrawal procedure. Reinforcing effects were evaluated in a third group of 12 rats with a history of remifentanil self-administration.

Results: BOM produced morphine-lever responding and both discriminative stimulus and rate-decreasing effects were antagonized by naltrexone. BOM did not markedly increase tail-withdrawal latencies from water maintained at 50 °C and did not substantially attenuate the antinociceptive effects of morphine. BOM was not self-administered and did not change remifentanil self-administration.

Conclusions: Some effects of BOM (e.g., discriminative stimulus effects) appear to be mediated by μ opioid receptors; however, BOM is not self-administered by rats, suggesting that it might have limited abuse liability and a reduced profile of adverse effects compared with currently prescribed opioids.

Keywords: Antinociception; BOM; Benzylideneoxymorphone; Drug discrimination; Rats; Self-administration.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Male
  • Morphine / pharmacology
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Oxymorphone / analogs & derivatives*
  • Oxymorphone / pharmacology
  • Pain / drug therapy*
  • Pain Measurement / drug effects
  • Rats
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Receptors, Opioid, mu / agonists*
  • Reinforcement, Psychology
  • Self Administration

Substances

  • 7-benzylideneoxymorphone
  • Analgesics, Opioid
  • Narcotic Antagonists
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Naltrexone
  • Morphine
  • Oxymorphone