Ivermectin toxicity in Collies
The phenomenon of ivermectin toxicity in Collies was first described in
1983. Ivermectin causes neurologic toxicity in some, but not all Collies, at
doses that are 1/200th of the dose required to cause toxicity in other dogs.
Neurologic manifestations of ivermectin in susceptible dogs include,
hypersalivation, ataxia, blindness, coma, respiratory compromise, and death.
A test is now available for drug
sensitivity.
Despite numerous investigations during the 1980's and 1990's, the cause of
this peculiar breed susceptibility was not elucidated. Recently, a
veterinarian at WSU discovered that the cause of ivermectin sensitivity in
Collies is a deletion mutation in the MDR1 gene. The MDR1 gene encodes a
large transmembrane protein, P-glycoprotein, that is an integral part of the
blood-brain barrier. P-glycoprotein functions in a protective capacity to
transport a variety of drug substrates, including ivermectin, from brain
tissue back into capillaries. Other drugs that are substrates for
P-glycoprotein include loperamide (Immodium®), digoxin, ondansetron, many
chemotherapeutic drugs including vincristine, vinblastine, and doxorubicin,
and other drugs. Collies have been documented to be susceptible to
neurotoxicity induced by some of these drugs also.
A test is now available to
determine if Collies are homozygous for the deletion mutation (i.e., display
the ivermectin-sensitive phenotype), heterozygous for the deletion mutation
(carriers) or homozygous for the normal gene sequence.
Ongoing research is directed at determining if other breeds that have been
reported to be sensitive to ivermectin (Australian Shepherds, Shelties,
Border Collies, and Old English Sheepdogs) have a similar mutation.
