Acepromazine,acetopromazine, oracetylpromazine (commonly known asACP,Ace, or by the trade namesAtravet orAcezine 2, number depending on mg/ml dose) is aphenothiazine derivativeantipsychotic drug. It was used in humans during the 1950s as anantipsychotic,[4] but is now almost exclusively used onanimals as asedative andantiemetic. A closely related analogue,chlorpromazine, is still used in humans.
The standard pharmaceutical preparation, acepromazine maleate, is used inveterinary medicine in dogs and cats. It is used widely in horses as a pre-anesthetic sedative and has been shown to reduce anesthesia related death.[5] However, it should be used with caution (but is not absolutelycontraindicated) in stallions due to the risk ofparaphimosis andpriapism.[6] Its potential for cardiac effects can be profound, namelyhypotension due to peripheral vasodilation, so it should be avoided or used with caution in geriatric or debilitated animals.[7]
The clinical pharmacology of acepromazine is similar to that of other phenothiazine derived anti-psychotic agents. The primary behavioral effects are attributed to its potent antagonism of post-synapticD2 receptors and, to a lesser degree, the otherD2-like receptors. Additional effects are related to its appreciable antagonistic effects on various other receptors, including theα1-adrenergic receptors,H1 receptors, andmuscarinic acetylcholine receptors. It is metabolized by the liver, oxidized to produce its primary metabolite, hydroxyethylpromazine sulfoxide, which is then excreted in the urine.[8][9]: 115 Its action at thechemoreceptor trigger zone (in thearea postrema) and thesolitary nucleus (in themedulla oblongata) allow it to have an antiemetic effect.[10][11]
Acepromazine is used as a sedative, pre-anaesthetic, anaesthetic adjunct, and tranquiliser. Acepromazine can commonly causeataxia and rarely can cause tremors anddystonia.[12]
The most common uses of acepromazine in animals are as an oral sedative before stressful events (such as thunderstorms), an injectable tranquilizer for particularly aggressive or fractious animals, and in combination with analgesics and other sedatives. It is also labeled for use in preventing motion sickness, as it has ananti-emetic effect in small animals.[13] It takes effect in about 10 minutes and lasts for 4–6 hours in small animals.[12]
While acepromazine is also used in cats, its absorption is erratic and can vary between individuals. It also generally induces less sedation than in dogs.[14][15] It also causes spontaneous motor activity (in both cats and dogs, but more often in cats) by blocking dopamine receptors in thestriatum andsubstantia nigra.[16]
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[9]: 116 [17] 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.[18] 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.[19] 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.
Acepromazine and its major metabolite, hydroxyethylpromazine sulfoxide (aka 2-(1-hydroxyethyl) promazine sulfoxide).[8][14][20]
In some boxers, acepromazine can causevasovagal syncope (due to a decreased stimulation of thesympathetic nervous system) andhypotension (due tovasodilation), leading to collapse.[21] 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.[16] Individual dogs of any breed can have a profound reaction characterized by hypotension, especially if there is an underlying heart problem.
Ingiant-breed dogs andsighthounds, the sedative effects of acepromazine may last for 12–24 hours, which is much longer than the usual 3–4 hours.[17][21]
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,[9]: 41–58 such as acepromazine andivermectin.[22] This protein is encoded by theABCB1 gene (previously known as theMDR1 gene). A mutation inABCB1 prevents P-gp from being correctly produced, so that dogs with this mutation have an increased sensitivity to drugs (such as acepromazine) which are substrates of P-gp.[22] Dogs which areheterozygous (that is, which have one functioningABCB1 gene, and one non-functioning gene) are less sensitive to acepromazine than dogs which arehomozygous (that is, which have two copies of the mutant gene). 75% ofCollies carry the mutatedABCB1 gene, as do 50% ofAustralian Shepherds. Other affected breeds include: Border Collie, English Shepherd, German Shepherd, Old English Sheepdog, and Sighthounds, shelties, long haired greyhound.[22]
Inequine surgery, premedication with acepromazine has been shown to reduce the perianaesthetic mortality rate, possibly due to its actions as asedative andanxiolytic.[5] It is less effective as a sedative if the horse is already excited.[24]
Additionally, acepromazine is used as avasodilator in the treatment oflaminitis, where an oral dose equivalent to "mild sedation" is commonly used, although the dose used is highly dependent on the treating veterinarian. While it is shown to elicit vasodilation in the distal limb, evidence showing its efficacy at increasing perfusion in the laminae is lacking. It is also sometimes used to treat a horse experiencingequine exertional rhabdomyolysis.[7]
Acepromazine has a withdrawal time of 7 days for meat and 48 hours for milk in the United States.[12]
Acepromazine also lowers blood pressure, and should therefore be used with caution in horses that are experiencinganemia,dehydration,shock, orcolic. It should not be used in horses dewormed withpiperazine.[24]
^abDugdale AH, Taylor PM (May 2016). "Equine anaesthesia-associated mortality: where are we now?".Veterinary Anaesthesia and Analgesia.43 (3):242–255.doi:10.1111/vaa.12372.PMID26970940.
^Valverde A, Cantwell S, Hernández J, Brotherson C (April 2003). "Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs".Veterinary Anaesthesia and Analgesia.30 (2): 99.doi:10.1046/j.1467-2995.2003.01331.x.PMID28404438.
^Tobias KM, Marioni-Henry K, Wagner R (July 1, 2006). "A retrospective study on the use of acepromazine maleate in dogs with seizures".Journal of the American Animal Hospital Association.42 (4):283–289.doi:10.5326/0420283.PMID16822767.
^McConnell J, Kirby R, Rudloff E (2007). "Administration of acepromazine maleate to 31 dogs with a history of seizures".Journal of Veterinary Emergency and Critical Care.17 (3):262–7.doi:10.1111/j.1476-4431.2007.00231.x.
^abcMealey KL (September 2013). "Adverse drug reactions in veterinary patients associated with drug transporters".The Veterinary Clinics of North America. Small Animal Practice.43 (5):1067–1078.doi:10.1016/j.cvsm.2013.04.004.PMID23890239.S2CID1780375.
