MDR1 Deficiency in Dogs: Drug Intolerance &

What is the MDR1 defect in dogs?

The MDR1 defect (also known as the ABCB1 mutation) is a genetic variation that causes severe hypersensitivity to a range of medications in certain dog breeds. The MDR1 gene (multidrug resistance gene 1), which encodes a transport protein (P-glycoprotein) in the blood-brain barrier, is affected. This protein pumps foreign substances—including many medications—from the brain tissue back into the blood.

Dogs with the MDR1 mutation (homozygous: both copies of the gene affected) lack this protective mechanism. Drugs that normally barely cross the blood-brain barrier accumulate in the brain—with severe neurotoxic effects, some of which are life-threatening.

Background + Scientific Context

Mealey et al. (2001, Pharmacogenetics, PubMed 11668219) were the first to identify the causative deletion in the mdr1 gene (a 4-base-pair deletion) in Collies as the basis for their known sensitivity to ivermectin: The mutation results in a non-functional transport protein. Ivermectin, at doses that are safe for normal dogs, accumulates in the brains of dogs that are homozygous for the mutation and causes central nervous system toxicity, potentially leading to coma. Collies, Shetland Sheepdogs, and related breeds are predisposed.

Mealey and Meurs (2008, Journal of the American Veterinary Medical Association, PubMed 18558882) investigated the breed distribution of the ABCB1 mutation in over 5,000 dogs: Affected breeds include, in addition to Collies, Australian Shepherds, Border Collies, McNabs, Old English Sheepdogs, Longhaired Whippets, and various mixed-breed dogs of Collie descent. Heterozygous dogs (one mutated copy) exhibit intermediate sensitivity—relevant for dose considerations.

Gramer et al. (2011, Veterinary Journal, PubMed 20167517) determined mutation frequencies in European Collie populations: In German and Austrian Rough Collie populations, over 50% of the dogs carried at least one mutated copy of the gene; approximately 25% were homozygous. This shows that the MDR1 defect in Collie-related breeds is not a rare exception, but rather an epidemiologically relevant problem.

Vitomalia-Position

The MDR1 defect is a clear argument for genetic screening prior to medication in Collie breeds. The standard adage “the dose makes the poison” applies here only to a limited extent: dosages that are harmless to unaffected dogs can be fatal to MDR1-homozygous animals. Every Collie, Australian Shepherd, or related breed should be tested—and the test results should be included in the medical record.

When does the MDR1 defect become a factor?

• Before administering antiparasitic drugs to affected breeds (ivermectin, high-dose milbemycin oxime, moxidectin)
• Before administering MDR1-substrate drugs: loperamide, vincristine, cyclosporine, digoxin, doxorubicin
• Before surgical procedures (anesthetics)
• In cases of unexplained neurological symptoms following medication
• Breeding Planning: MDR1 Status in the Breeding Program

Practical application

Breeds with a high frequency of the MDR1 mutation:

MDR1-related drugs (substrate list): - Antiparasitic drugs: Ivermectin (Caution: dosage!), Milbemycin oxime (high dose), Moxidectin (high dose) - Gastrointestinal medications: Loperamide (Imodium) — even therapeutic doses are neurotoxic in MDR1 dogs - Anticancer drugs: Vincristine, doxorubicin, vinblastine — check MDR1 status during cancer treatment - Others: Cyclosporine, digoxin, acepromazine (use with caution)

Genetic testing: - Buccal swab, sent to specialized laboratories (e.g., Laboklin, University of Veterinary Medicine Hannover) - Result: normal/normal (+/+), carrier (+/-), affected (-/-) - One-time test; no follow-up test required

Common Mistakes & Myths

• “My collie has never had any problems—he’s not affected.” Previous tolerance does not prove that a dog is not affected. MDR1 issues occur specifically with certain substances and dosages; without exposure, there are no symptoms.
• "The amount of ivermectin in standard deworming medications is too low to be dangerous." Antiparasitic sprays for horses and dosages for livestock are often ten times higher than those for dogs—accidental ingestion (horse feces after ivermectin treatment) has killed MDR1-positive dogs.
• “Only Collies are affected.” Mixed-breed dogs with Collie ancestry may also carry the mutation—so if a dog’s lineage is unknown, it’s a good idea to have it tested.

Current State of Research (2026)

MDR1/ABCB1 is one of the best-characterized pharmacogenetic traits in dogs. Genetic tests are routinely available and affordable. Awareness in veterinary practice has increased; nevertheless, MDR1 dogs are still regularly treated with contraindicated substances. Washington State University (WSU) maintains an up-to-date database of the MDR1 substrate list; veterinarians can use it to determine safe dosages.

Frequently Asked Questions

Which breeds are affected by the MDR1 defect?

Primarily Collie-related herding dog breeds: Rough/Smooth Collie, Shetland Sheepdog, Australian Shepherd, McNab, Border Collie, Longhaired Whippet, Old English Sheepdog. Crossbreeds of these breeds may also be affected. The following applies to all these breeds: genetic testing should be performed before administering MDR1 substrates for the first time.

How do I get my dog tested for MDR1?

The test is performed using a buccal swab (taken from the inner cheek), which is sent to a specialized laboratory. In Germany, laboratories such as Laboklin and the University of Veterinary Medicine Hannover offer this test. A veterinarian can order the test; the cost is approximately €50–80. The result is valid for life.

Is loperamide (Imodium) dangerous for my Collie?

Yes — Loperamide is a classic MDR1 substrate. In MDR1-homozygous dogs, it accumulates in brain tissue and can cause severe neurotoxicity (sedation, ataxia, coma) — even at standard doses. Do not use loperamide in Collie breeds without first performing an MDR1 test.

Related terms

• Medications for Dogs
• Ivermectin for Dogs
• Genetic testing for dogs
• Collie (dog breed)
• Parasite prevention for dogs

Sources & Further Reading

1. Mealey, K. L., Bentjen, S. A., Gay, J. M., & Cantor, G. H. (2001). Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics, 11(8), 727–733. https://pubmed.ncbi.nlm.nih.gov/11668219/

2. Mealey, K. L., & Meurs, K. M. (2008). Breed distribution of the ABCB1-1Delta (multidrug sensitivity) polymorphism among dogs undergoing ACTH stimulation testing for hypoadrenocorticism. Journal of the American Veterinary Medical Association, 233(6), 921–924. https://pubmed.ncbi.nlm.nih.gov/18558882/

3. Gramer, I., Leidolf, R., Döring, B., Klintzsch, S., Krämer, E.-M., Yalcin, E., … Geyer, J. (2011). Breed distribution of the nt230(del4) MDR1 mutation in dogs. Veterinary Journal, 189(1), 67–71. https://pubmed.ncbi.nlm.nih.gov/20167517/