Multidrug resistance and the MDR1 mutation in dogs

by Dr. Mikel Delgado, PhD

Medications are intended to treat, prevent, or manage conditions that can range from annoying to possibly even life threatening. But due to a mutation in a gene called MDR1, some dogs are extremely sensitive to certain medications. Dogs affected by this mutation may experience medication side effects that are not observed in other dogs. In some cases, reaction to the medication can even be deadly.

The MDR1 gene codes for a protein called p-glycoprotein, which pumps toxins and chemicals out of cells. P-glycoprotein also prevents medications from crossing the blood-brain barrier, a collection of tightly connected cells that protects the brain from toxins and pathogens. 

A dog with two functional copies of the MDR1 gene has a normal p-glycoprotein system, and will respond in a predictable manner to prescribed medications when dosed appropriately. Dogs with one or two copies of the MDR1 mutation have reduced p-glycoprotein function, which means that medications are not correctly metabolized and stay in the system for a longer period. These drugs reach higher levels in the cells of the body, and in some cases may enter the brain, leading to neurological effects.

Medications that may be problematic for dogs with the MDR1 mutation

The most common medications that are affected by the MDR1 mutation include:

• Some antiparasitic drugs such as ivermectin, selamectin, milbemycin and moxidectin
• Chemotherapy drugs such as doxorubicin, vinblastine and vincristine
• Sedatives such as Acepromazine
• Pain medications such as Butorphanol
• Some antibiotics such as erythromycin
• Loperamide (Imodium)

Although ivermectin is on the list, routine use of ivermectin products designed for dogs to prevent heartworm is not considered problematic for dogs carrying the MDR1 mutation. It is only at higher doses (e.g., off label use of products made for livestock) that ivermectin should be avoided. It should also be noted that the MDR1 mutation is not related to vaccine reactions. Talk to your veterinarian if you have any questions about whether your dog might be at risk and how that might affect any prescriptions for your dog.

Signs of drug toxicosis in dogs

Depending on the medication, side effects can range from lethargy, disorientation and weakness to more serious reactions, including loss of consciousness.

If you think your dog is experiencing drug toxicosis, they should be evaluated by a veterinarian immediately. Some medications may have reversal agents, but most dogs will need intensive care, such as intravenous fluids and nutritional support. 

Dog breeds affected

Herding and sighthound breeds appear to be the most likely carriers of MDR1 mutations. Approximately 70% of Collies carry at least one mutation. Whippets and Australian Shepherds are also commonly affected. Mixed-breed dogs, especially with herding ancestry, may also have the mutation.

MDR1 Mode of inheritance

Multi-drug resistance is caused when a dog has one or two mutations of the MDR1 gene. Dogs inherit one copy of the gene from each parent. If both parents pass down functional copies of the gene, the dog will not be affected. A dog who inherits one or two copies of the MDR1 mutation will be at risk, but dogs with two copies of the mutation are more susceptible.

What you can do to protect your dog

• Ask your breeder if they tested their breeding dogs and if they are clear or carriers of the MDR1 gene
• Get your dog(s) tested for the MDR1 mutation
• Let your vet know about your dog’s MDR1 testing status
• If your dog has one or more MDR1 mutation, place a tag on them in case of emergency to notify anyone who might be caring for your dog

For further information:

VCA: Multidrug Resistance Mutation (MDR1)

Breed distribution and history of canine mdr1-1Δ, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage

MDR1 Affected Breeds