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

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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.

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Funding

These studies were supported by Welch Foundation Grant AQ-0039 (CPF) and the Concordia University Wisconsin School of Pharmacy (CWC).

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Authors and Affiliations

  1. Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr.—mail code 7764, San Antonio, TX, 78229-3900, USA

    Sanjana Mada, Lisa R. Gerak, Amélie Soyer, David R. Maguire, Zehua Hu, Vanessa Minervini & Charles P. France

  2. Addiction Research, Treatment & Training Center of Excellence, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr.—mail code 7764, San Antonio, TX, 78229-3900, USA

    Sanjana Mada, Lisa R. Gerak, Amélie Soyer, David R. Maguire, Zehua Hu, Vanessa Minervini & Charles P. France

  3. Department of Pharmaceutical Sciences, School of Pharmacy, Concordia University Wisconsin, 12800 N. Lake Shore Drive, PH 239, Mequon, WI, 53097, USA

    Christopher W. Cunningham

  4. Department of Psychiatry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr.—mail code 7764, San Antonio, TX, 78229-3900, USA

    Charles P. France

Authors
  1. Sanjana Mada
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  2. Lisa R. Gerak
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  3. Amélie Soyer
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  4. David R. Maguire
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  6. Vanessa Minervini
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  7. Christopher W. Cunningham
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  8. Charles P. France
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Correspondence to Charles P. France.

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Mada, S., Gerak, L.R., Soyer, A. et al. Behavioral effects of benzylideneoxymorphone (BOM), a low efficacy µ opioid receptor agonist and a δ opioid receptor antagonist. Psychopharmacology 237, 3591–3602 (2020). https://doi.org/10.1007/s00213-020-05638-1

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  • DOI: https://doi.org/10.1007/s00213-020-05638-1

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