Dogs that carry this mutation are asymptomatic until they are exposed to a medication that uses the pump that is rendered defective by the mutation in the MDR1 (also called ABCB1) gene. Drugs known to use this P-glycoprotein pump are macrocyclic lactones (antiparasitic drugs), loperamide (antidiarrheal), erythromycin (antibiotic), acepromazine (tranquilizer), butorphanol (opioid), and certain drugs used in cancer treatment (vincristine, vinblastine, and doxorubicin). When these medications are administered, they accumulate in the brain which results in the adverse reactions. Typical symptoms include tremors, loss of balance, seizures, obtundation, excessive salivation, dilated pupils, and bradycardia. If untreated, the condition may lead to respiratory arrest, coma or death. Because dogs with one copy of the mutation will have some P-glycoprotein function, the most severe cases tend to occur in dogs that have two copies of the mutation and therefore lack any functional P-glycoprotein pumps. However, the condition can still be very severe in dogs that have only one copy of the mutation.

For dogs with copies of the MDR1 mutation it is important to be aware of medications which may result in an adverse reaction. These include: Acepromazine, Butorphanol, Doxorubicin, Doramectin, Emodepside, Erythromycin, Ivermectin, Loperamide, Milbemycin, Moxidectin, Paclitaxel, Rifampin, Selamectin, Vinblastine, Vincristine. It is best to explore alternative medications that will not use this P-glycoprotein pump or, at minimum, consider reduction of the dose to levels safe for an MDR1 positive dog.

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

This disease is autosomal dominant meaning that one copy of the mutation is needed for signs of this disorder to occur. For some breeds where the MDR1 mutation frequency is particular high, breeders may consider matings using dogs that have one or two copies of the MDR1 mutation to maintain genetic diversity within their breed. IMPORTANT: Resulting puppies must be tested for the MDR1 mutation to ensure safe future medical treatment. If a dog with one copy of the MDR1 mutation is bred with a clear dog with no copies of the MDR1 mutation, about half of the puppies will have one copy and half will have no copies of the MDR1 mutation. If a dog with two copies of the MDR1 mutation is bred with a clear dog, the resulting puppies will all have one copy of the mutation. Please note: It is possible that disease signs similar to the ones caused by the MDR1 mutation could develop due to a different genetic or clinical cause.