MDR1 Gene


The following information is from an article published by the Washington State University Veterinary Clinical Pharmacology Laboratory in 2007. You can read the entire article at;

MDR1 information


Please note: The importance of this article is due to the high use of Heartguard for controlling and preventing heartworm. Dogs with the mutant MDR1 gene can have adverse reactions to the amount of Ivermectin in Heartguard. (Literature from the manufacturer of Heartguard states that the amount of ivermectin in their product is not high enough to effect an MDR1 sensitive dog)


As a breeder, I recommend that you use an alternative heartworm preventative such as Interceptor or Revolution, which have a lower dose of Ivermectin and should not adversely affect dogs with the mutant MDR1 gene. If you want to be sure whether or not your dog has the mutant gene, gene testing can be done. Contact your veterinarian for more information.


It is well known that Collies and related breeds can have adverse reactions to drugs such as Ivermectin, Loperamide. It has been determined that these breeds have this problem due to a mutation in the multi-drug resistance gene (MDR1). This gene encodes a protein that is responsible for pumping many drugs out of the brain. Dogs with the mutant gene cannot pump some drugs out of the brain as a normal dog would. The result may be an illness requiring an extended hospital stay or death.


This mutation has been found in Collies, Shetland Sheepdogs, Australian Shepherds, Old English Sheepdogs, German Shepherds, Long-haired Whippets, Silken Windhounds, and a number of mixed breed dogs.


There are many different types of drugs that have been reported to cause problems. The following is a current list of these drugs, however, please check with the veterinary college for updated lists.

Ivermectin (found in heartworm medications)
Loperamide (Imodium over the counter antidiarrheal agent)
Doxorubicin, Vincristine, Vinblastine (anticancer agents)
Cyclosporin (immunosuppressive agent)
Digoxin (heart drug)
Acepromazine (tranquilizer)
Butorphanol ("Bute" pain control)

The following drugs may also cause problems;

Ondansetron, Domperidone, Paclitaxel, Mitoxantrone, Etoposide, Rifampicin, Quinidine, Morphine


There are two solutions to the effects of the MDR1 gene. You can have your dog tested for the gene. If the dog is N/N you have no sensitivity, otherwise it is recommended that you stay away from the above drugs. The other is to simply avoid these drugs unless they are necessary to the health of your dog, then test for the gene.