The ABCB1 gene (formerly MDR1) encodes P-glycoprotein, an efflux pump of the blood-brain barrier that prevents numerous drugs from reaching the central nervous system. When the gene does not function, certain medications (ivermectin and other macrocyclic lactones, loperamide, some chemotherapeutic agents) reach toxic concentrations in the brain, with severe neurotoxicity that can be fatal. In the cat, the evidence on specific ABCB1 variants is more limited than in the dog.

In the dog the classic deletion reaches high frequencies in the Collie and related breeds. In the cat the population frequency is not established: in the original study the deletion was rare (1 affected homozygous cat and 4 non-phenotyped cats).

- Ataxia and depression after administration of the drug\n- Mydriasis\n- Tremors and salivation\n- Seizures\n- Coma and death in severe intoxications\n- Signs appear between hours and one or two days after the dose

Ivermectin sensitivity was classically described in Collies and herding breeds; in 2001 a 4-base-pair deletion in ABCB1 was identified in the dog as the cause. In 2015, Mealey and Burke described in the cat a 2-base-pair deletion (c.1930_1931delTC) in a cat with ivermectin toxicity; most of the cats with an adverse reaction in that study did not carry the variant, so the feline test should be interpreted with caution and together with the clinical picture.

- Communicate the result to all veterinarians involved and note it in the health record.\n- Avoid or adjust the dose of ivermectin and macrocyclic lactones in general, loperamide and chemotherapeutic agents that are substrates of P-glycoprotein (e.g. vincristine, doxorubicin), always under veterinary protocol.\n- For deworming, choose alternatives with a proven safety margin in cats and at labelled doses.\n- It is not grounds for reproductive exclusion in itself: it is a pharmacogenetic trait managed clinically.

Differentiate ABCB1 neurotoxicity from other causes of acute neurological signs: pyrethroid or permethrin poisoning (common in cats), metabolic encephalopathies and epilepsy. Permethrin is toxic to all cats because of their glucuronidation deficit, regardless of ABCB1: never use dog antiparasitic products on cats. In case of exposure, urgent decontamination and supportive treatment.

1. Mealey KL, et al. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics. 2001;11(8):727-733. PMID: 11692082
2. Mealey KL, Burke NS. Identification of a nonsense mutation in feline ABCB1. J Vet Pharmacol Ther. 2015;38(5):429-433. PMID: 25660379
3. Mealey KL. Canine ABCB1 and macrocyclic lactones: heartworm prevention and pharmacogenetics. Vet Parasitol. 2008;158(3):215-222. PMID: 18922637