Ivermectin Sensitivity MDR1

What is Ivermectin Sensitivity MDR1 in dogs?

P-glycoprotein photoOriginally, thought to be specific to the drug Ivermectin, Ivermectin Sensitivity MDR1 is actually a disease characterised by adverse reactions to multiple drugs by an affected dog. This is an inherited disease that has an autosomal recessive pattern of inheritance. Affected dogs produce a very diminished level of a specific protein called P-glycoprotein. This protein is an essential part of the blood-brain barrier that limits entry of specific drugs and other compounds into the central nervous system. Dogs affected by Ivermectin Sensitivity MDR1, cannot remove these drugs from their central nervous system were these drugs accumulate in the central nervous system causing problems for the dog.

Genetics of Ivermectin Sensitivity MDR1

Ivermectin Sensitivity MDR1 is a result of a defect (mutation) in the MDR1 (also called the ABCB1) gene that causes the dysfunction of a protein called P-glycoprotein. As an autosomal recessive trait, the condition can be passed on from 2 parents that are either carriers or affected by the condition. A clear parent (a dog with 2 normal copies of the gene) will not pass on the full condition to their offspring regardless of what dog they are bred with. Many carrier dogs can still be affected by the same drugs as affected dogs at high dosages of the drugs as they still produce P-glycoprotein, but at lower levels than clear dogs.

Severity of Ivermectin Sensitivity MDR1 in dogs

Ivermectin Sensitivity MDR1 is of medium severity as it only damages affected dogs if they are given any of the drugs that will accumulate in the central nervous system. Affected dogs given normally safe doses of these drugs can have a range of reactions from minor adverse effects to death.

What are the symptoms of Ivermectin Sensitivity MDR1 in dogs?

Symptoms of Ivermectin Sensitivity MDR1 vary depending on what drugs are given and in what quantities to the affected dog. Symptoms can be allergic reaction-like in the affected dog, but most of the time they are neurological in nature. These include symptoms ranging from mild to excessive salivation, tremors, ataxia (a lack of voluntary muscle control during walking for example), blindness, deafness, anorexia, coma and even death.

Diagnosis of Ivermectin Sensitivity MDR1 in dogs

Sadly, the most common diagnosis of Ivermectin Sensitivity MDR1 happens after the dog has already been given one of the common drugs that they are sensitive to and had a reaction. Modern DNA Disease Screening for the mutated MDR1/ABCB1 gene can test dogs for their sensitivity to these drugs before they are administered.

Treatment of dogs with Ivermectin Sensitivity MDR1

Ivermectin HeartgardTreatment is normally supportive care of the Ivermectin Sensitivity MDR1 affected dog once they have had a reaction to one of the specific drugs. Preventing the use of these drugs is the best way to protect affected dogs from having any reactions. Aside from Ivermectin for which the condition was originally named, the other drugs include acepromazine, doxorubicin, butorphanol, vincristine, emodepside, moxidectin, metronidazole, loperamide, rifampin, selamectin, milbemycin, vinblastine and erythromycin. Dogs, being dogs, will often eat the faeces of other animals and care must be taken around the faeces of other animals treated with these drugs as the residue in the faeces can be enough to cause serious effects in dogs affected by Ivermectin Sensitivity MDR1. This is especially so with Ivermectin, which is commonly used as a worming treatment for horses and other livestock.


Alves L, Hulsmeyer V, Jaggy A, Fischer A, Leeb T, Drogemuller M. Polymorphisms in the ABCB1 gene in phenobarbital responsive and resistant idiopathic epileptic border collies. J Vet Intern Med. 2011 May-Jun;25(3):484-9. 

Barbet JL, Snook T, Gay JM, Mealey KL. (2009) ABCB1-1 Delta (MDR1-1 Delta) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis. Vet Dermatol. 2009 Apr;20(2):111-4

Geyer J, Doring B, Godoy JR, Leidolf R, Moritz A, Petzinger E. (2005) Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany. J Vet Pharmacol Ther.28(6):545-51

Geyer, J., Doring, B., Godoy, J. R., Moritz, A., Petzinger, E. (2005). Development of a PCR-based diagnostic test detecting a nt230(del4) MDR1 mutation in dogs: verification in a moxidectin-sensitive Australian Shepherd. J. vet. Pharmacol. Therap.28, 95-99

Gramer I, Leidolf R, Döring B, Klintzsch S, Krämer EM, Yalcin E, Petzinger E, Geyer J. Breed distribution of the nt230(del4) MDR1 mutation in dogs. Vet J. 2010 Jul 21

Gustafson DL & Thamm DH (2010) Pharmacokinetic modeling of doxorubicin pharmacokinetics in dogs deficient in ABCB1 drug transporters. J Vet Intern Med 24(3):579-586

Klintzsch S, Meerkamp K, Döring B, Geyer J. (2009) Detection of the nt230[del4] MDR1 mutation in dogs by a fluorogenic 5′ nuclease TaqMan allelic discrimination method. Vet J. 2009 Sep 2

Mealey KL, Bentjen SA, Waiting DK. (2002)Frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample population of collies from the northwestern United States. American Journal of Veterinary Research. 63(4):479-81

Mealey KL, Meurs KM, (2008) Breed distribution of the ABCB1-1Delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping. J Am Vet Med Assoc. 233(6):921-4

Merola VM & Eubig PA (2012) Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-glycoprotein in dogs and cats. Vet Clin North Am Small Anim Pract 42(2):313-333

Mizukami K, Chang H, Yabuki A, Kawamichi T, Hossain MA, Rahman MM, Uddin MM, Yamato O. Rapid genotyping assays for the 4-base pair deletion of canine MDR1/ABCB1 gene and low frequency of the mutant allele in border collie dogs. J Vet Diagn Invest. 2012 Jan;24(1):127-34

Neff MW, Robertson KR, Wong AK, Safra N, Broman KW, Slatkin M, Mealey KL, Pedersen NC. (2004) Breed distribution and history of canine mdr1-1Delta, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage. Proc Natl Acad Sci U S A. 101(32):11725-30

Nelson OL, Carsten E, Bentjen SA, Mealey KL. (2003) Ivermectin toxicity in an Australian Shepherd dog with the MDR1 mutation associated with ivermectin sensitivity in Collies. J Vet Intern Med. 17(3):354-6

buy facebook likes