# Case Report: Adverse reaction to butorphanol in a Collie homozygous for the ABCB1-1∆ (MDR1) mutation

**Authors:** Tyler S. Nelson, Heather N. Allen, April Hardison, Erin Miscioscia, Rajesh Khanna, Elizabeth A. Maxwell

PMC · DOI: 10.3389/fvets.2025.1603375 · Frontiers in Veterinary Science · 2025-05-29

## TL;DR

A Collie with a specific genetic mutation had a severe reaction to a drug, highlighting the need for genetic screening in veterinary medicine.

## Contribution

This case report highlights the first documented severe neurotoxic reaction to butorphanol in a Collie with the ABCB1-1∆ mutation.

## Key findings

- A Collie homozygous for ABCB1-1∆ mutation experienced severe neurotoxicity after butorphanol administration.
- Continuous naloxone administration was required for 40 hours to manage symptoms.
- Metoclopramide and maropitant may have worsened the neurotoxic effects.

## Abstract

Certain dog breeds, particularly herding breeds like Collies, are predisposed to drug sensitivity due to the ABCB1-1∆ (previously known as MDR1) mutation, which disrupts P-glycoprotein (P-gp) function. This mutation impairs drug efflux at the blood–brain barrier, leading to increased susceptibility to neurotoxic effects. While adverse reactions to P-gp substrate drugs such as macrocyclic lactones and chemotherapeutics are well documented, opioid sensitivity remains poorly understood. This case report documents a Collie that developed severe neurotoxicity, including profound sedation, ataxia, hypersalivation, and seizures, following a single 0.2 mg/kg dose of butorphanol. Symptoms persisted despite supportive care, requiring continuous naloxone administration for approximately 40 h before significant improvement. Neurotoxicological effects may have been exacerbated by metoclopramide and maropitant, known P-gp substrates. This case underscores the need for further research into opioid pharmacokinetics in ABCB1-1∆ mutant dogs and highlights the importance of genetic screening in veterinary practice. To enhance patient safety, integration of automated alerts within electronic medical record systems is recommended to flag high-risk drugs for at-risk breeds, providing real-time warnings, dosing adjustments, and monitoring guidance. These measures could reduce adverse drug reactions and improve clinical outcomes in genetically susceptible dogs.

## Linked entities

- **Genes:** ABCB11 (ATP binding cassette subfamily B member 11) [NCBI Gene 8647], ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243]
- **Proteins:** Mdr65 (Multi drug resistance 65), PGP (phosphoglycolate phosphatase)
- **Chemicals:** butorphanol (PubChem CID 5361092), naloxone (PubChem CID 4425), metoclopramide (PubChem CID 4168), maropitant (PubChem CID 204108)

## Full-text entities

- **Genes:** ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 403879] {aka MDR1, p-gp}, ABCB11 (ATP binding cassette subfamily B member 11) [NCBI Gene 488390] {aka Abcb11e, BSEP}, P-glycoprotein [NCBI Gene 610926]
- **Diseases:** ataxia (MESH:D001259), seizures (MESH:D012640), hypersalivation (MESH:D012798), neurotoxic (MESH:D020258)
- **Chemicals:** maropitant (MESH:C518176), naloxone (MESH:D009270), macrocyclic lactones (-), butorphanol (MESH:D002077), metoclopramide (MESH:D008787)
- **Species:** Homo sapiens (human, species) [taxon 9606], Canis lupus familiaris (dog, subspecies) [taxon 9615]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12159028/full.md

## References

22 references — full list in the complete paper: https://tomesphere.com/paper/PMC12159028/full.md

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Source: https://tomesphere.com/paper/PMC12159028