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MDR1 Medication Sensitivity

MDR1 Medication Sensitivity is a disorder caused by a defect to a drug pumping protein that plays an important role in limiting drug absorption and distribution (particularly to the brain). Cats with the MDR1 variant may have severe adverse reactions to some commonly used medications.

Found in

1 in 68 cats

in our testing

Key Signs

Some medications may cause generalized neurologic abnormalities including Dilated pupils, Drooling, Difficulty breathing, Difficulty walking, Jumpiness, Tremors, Seizures, and Lethargy

Age of Onset

At birth

Present at birth

Inheritance

Autosomal Recessive

For autosomal recessive disorders, cats with two copies of the variant are at risk of developing the condition. Cats with one copy of the variant are considered carriers and are usually not at risk of developing the disorder. However, carriers of some complex variants grouped in this category may be associated with a low risk of developing the disorder. Individuals with one or two copies may pass the disorder-associated variant to their kittens if bred.

Likelihood of the Condition

High likelihood

At risk cats are highly likely to show signs of this disease in their lifetime.

What to Do

Here’s how to care for a cat with Multidrug Resistance 1

Partner with your veterinarian to make a plan regarding your cat’s well-being, including any insights provided through genetic testing. If your pet is at risk or is showing signs of this disorder, then the first step is to speak with your veterinarian.

For Veterinarians

Here’s what a vet needs to know about Multidrug Resistance 1

Cats with this variant are asymptomatic until exposed to a medication that uses the drug transport pump rendered defective by the mutation in the MDR1 (also called ABCB1) gene. Drugs known to use this P-glycoprotein pump are macrocyclic lactones including eprinomectin-containing products labeled for use in cats (antiparasitic drugs), loperamide (antidiarrheal), erythromycin (antibiotic), acepromazine (tranquilizer), butorphanol (opioid), certain drugs used in cancer treatment (vincristine, vinblastine, doxorubicin), and possibly others still to be determined. When these medications are administered, they accumulate in the brain which results in adverse reactions. Typical symptoms involve generalized neurologic dysfunction which may include mydriasis, dyspnea, tremors, hyperreactivity, ataxia or paresis. In more severe cases cats may experience seizures, coma and death. However, with appropriate supportive care by a veterinarian, most affected cats may be able to fully recover.

Research studies have shown that cats with two copies of the MDR1 Medication Sensitivity variant have altered drug responses and have suggested, in theory, that cats with one copy of the MDR1 Medication Sensitivity variant may also be affected if treated with higher doses of drugs known to be dependent on the P-glycoprotein pump. Therefore, the current recommendation when treating cats with this variant is to adhere to similar precautions recommended for dogs with the MDR1 variant. It is important to be aware of medications which may result in an adverse reaction. Known medications currently include: Acepromazine, Butorphanol, Doxorubicin, Doramectin, Emodepside, Eprinomectin, Erythromycin, Ivermectin, Loperamide, Milbemycin, Moxidectin, Paclitaxel, Rifampin, Selamectin, Vinblastine, Vincristine. Please note that while some antiparasitic medications are considered safe for cats with the MDR1 variant when used according to labeled instructions (e.g. ivermectin, milbemycin oxime), others may cause adverse reactions if ingested by mouth (e.g. selamectin, imadocloprid, fluralaner) and some, particularly eprinomectin-containing products, are not recommended for use in cats with the MDR1 variant. Therefore, cats with the MDR1 variant should not be treated with any eprinomectin-containing products. Please consult the product insert and manufacturer when clarification is needed. Unfortunately, there is no antidote when treating cats with macrocyclic lactone toxicosis due to this disorder. If the product was administered topically, the cat should be bathed to prevent further absorption of the product and then provide supportive care as indicated. With appropriate and timely care, most affected cats may be able to fully recover.

For Breeders

Planning to breed a cat with this genetic variant?

There are many responsibilities to consider when breeding cats. Regardless of test results it is important that your cat is in good general health and that you are in a position to care for the kittens if new responsible owners are not found. For first time or novice breeders, advice can be found at most cat registry websites.

Further research is needed to determine if cats with one copy of the variant may have altered drug responses. At this time, breeding cats with one or two copies of the MDR1 Medication Sensitivity variant should be approached with caution. If a cat with one copy of the MDR1 Medication Sensitivity variant is bred with a clear cat with no copies of the MDR1 Medication Sensitivity variant, on average half of the kittens will have one copy and half will have no copies of the MDR1 Medication Sensitivity variant. If a cat with two copies of the MDR1 Medication Sensitivity variant is bred with a clear cat with no copies of the MDR1 Medication Sensitivity variant, the resulting kittens will all have one copy of the MDR1 Medication Sensitivity variant. If litters are expected to contain kittens with the MDR1 Medication Sensitivity variant, the kittens should be DNA tested as they may show signs of sensitivity to some common medications. Carrier to carrier matings are not advised as the resulting litter may contain kittens with two copies of the MDR1 Medication Sensitivity variant, which is known to cause medication sensitivity. Please note: It is possible that clinical signs similar to the ones caused by the MDR1 Medication Sensitivity variant could develop due to a different genetic or clinical cause.

Technical Details

Gene ABCB1
Variant Deletion
Chromosome A2
Coordinate Start 93,144,356
Coordinate End 93,144,357

All coordinates reference FelCat9.0

References & Credit

Credit to our scientific colleagues:

Mealey, K. L., & Burke, N. S. (2015). Identification of a nonsense mutation in feline ABCB1. Journal of Veterinary Pharmacology and Therapeutics, 38(5), 429–433. View the article

Mealey, K. L., Burke, N. S. Rebecca, & Connors, R. L. (2021). Role of an ABCB1 1930_1931del TC gene mutation in a temporal cluster of macrocyclic lactone-induced neurologic toxicosis in cats associated with products labelled for companion animal use. J Am Vet Med Assoc . 2021 Jul 1;259(1):72-76 View the article

Mealey KL, Burke NS, Villarino NF, Court MH, Heusser JP. Application of eprinomectin-containing parasiticides at label doses causes neurological toxicosis in cats homozygous for ABCB11930_1931del TC. J Vet Pharmacol Ther. 2024 Feb 17. View the article

Nürnberger D, Wagner L, Müller SF, Leiting S, Leidolf R, Alber J, Hamann M, Geyer J. Detection of the ABCB11930_1931del TC Mutation in Two Suspected Ivermectin-Sensitive Cats and Their Relatives by a Novel TaqMan Allelic Discrimination Assay. Front Vet Sci. 2022 Feb 21;8:808392. View the article