causes spontaneous motor activity (in both cats and dogs, but more often in cats) by blocking dopamine receptors in the striatum and substantia nigra. Adverse effects in dogs Literature from the 1950s raised concerns about phenothiazine-induced seizures in human patients. For this reason, caution has typically been advised when contemplating acepromazine use in epileptic canine patients, as it was widely believed to lower the seizures threshold. More current studies, however, have failed to show a positive association between use of acepromazine and seizure activity and show a possible role for acepromazine in seizure control: in a retrospective study at University of Tennessee, acepromazine was administered for tranquilization to 36 dogs with a prior history of seizures and to decrease seizure activity in 11 dogs. No seizures were seen within 16 hours of acepromazine administration in the 36 dogs that received the drug, and the seizures abated for 1.5 to 8 hours (n=6) or did not recur (n=2) in eight of 10 dogs that were actively seizing. Excitement-induced seizures were reduced for 2 months in one dog. A second retrospective study also concluded that administration of acepromazine to dogs with prior or acute seizure history did not potentiate seizures, and there was some trend toward seizure reduction. The original seizure cautions reported in the 1950s were in human patients on relatively high doses of the antipsychotic chlorpromazine while the doses of acepromazine used in the two published veterinary studies cited above are much lower. In some boxers, acepromazine can cause vasovagal syncope (due to a decreased stimulation of the sympathetic nervous system) and hypotension (due to vasodilation), leading to collapse. This may occur only in certain families of boxers, but the unknown risk to an individual dog means that acepromazine should be used at reduced doses, or not at all, in this breed. Individual dogs of any breed can have a profound reaction characterized by hypotension, especially if there is an underlying heart problem. In giant-breed dogs and sighthounds, the sedative effects of acepromazine may last for 12–24 hours, which is much longer than the usual 3–4 hours. Dogs with a mutation in the ABCB1 (MDR1) gene P-glycoprotein (P-gp), also known as multidrug resistant protein 1 (MDR1), is a protein found in cell membranes which is important in the metabolism and excretion of some drugs, such as acepromazine and ivermectin. This protein is encoded by the ABCB1 gene (previously known as