Acepromazine

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Acepromazine
Acepromazine.svg
Clinical data
Trade names Atravet, Acezine 2
AHFS/Drugs.com International Drug Names
Routes of
administration 		IV, IM, SQ, oral [1] [2]
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 6.6 L/kg, high volume of distribution
Elimination half-life 3 hours in horses, 15.9 hours in canines
Excretion urine
Identifiers
  • 1-{10-[3-(Dimethylamino)propyl]-10H-phenothiazin-2-yl}ethanone
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.451 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H22N2OS
Molar mass 326.46 g·mol−1
3D model (JSmol)
  • O=C(c2cc1N(c3c(Sc1cc2)cccc3)CCCN(C)C)C
  • InChI=1S/C19H22N2OS/c1-14(22)15-9-10-19-17(13-15)21(12-6-11-20(2)3)16-7-4-5-8-18(16)23-19/h4-5,7-10,13H,6,11-12H2,1-3H3 Yes check.svgY
  • Key:NOSIYYJFMPDDSA-UHFFFAOYSA-N Yes check.svgY
   (verify)

Acepromazine, acetopromazine, or acetylpromazine (commonly known as ACP, Ace, or by the trade names Atravet or Acezine 2, number depending on mg/ml dose) is a phenothiazine derivative antipsychotic drug. It was used in humans during the 1950s as an antipsychotic, [4] but is now almost exclusively used on animals as a sedative and antiemetic. A closely related analogue, chlorpromazine, is still used in humans.

Contents

The standard pharmaceutical preparation, acepromazine maleate, is used in veterinary 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 absolutely contraindicated) in stallions due to the risk of paraphimosis and priapism. [6] Its potential for cardiac effects can be profound, namely hypotension due to peripheral vasodilation, so it should be avoided or used with caution in geriatric or debilitated animals. [7]

Pharmacology

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-synaptic D2 receptors and, to a lesser degree, the other D2-like receptors. Additional effects are related to its appreciable antagonistic effects on various other receptors, including the α1-adrenergic receptors, H1 receptors, and muscarinic 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 the chemoreceptor trigger zone (in the area postrema) and the solitary nucleus (in the medulla oblongata) allow it to have an antiemetic effect. [10] [11]

Veterinary use

Canine and feline

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. [12] Its effects as a CNS depressant means that fewer opiates are required to reach the same amount of sedation, and it prevents the arrhythmia and vomiting that many opiates induce.

Adverse effects in cats

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. [13] [14] It also causes spontaneous motor activity (in both cats and dogs, but more often in cats) by blocking dopamine receptors in the striatum and substantia nigra. [15]

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 [9] : 116  [16] 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. [17] 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. [18] 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). Acepromazine and metabolites.svg
Acepromazine and its major metabolite, hydroxyethylpromazine sulfoxide (aka 2-(1-hydroxyethyl) promazine sulfoxide).

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. [20] 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. [15] 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. [16] [20]

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, [9] : 41–58  such as acepromazine and ivermectin. [21] This protein is encoded by the ABCB1 gene (previously known as the MDR1 gene). A mutation in ABCB1 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. [21] Dogs which are heterozygous (that is, which have one functioning ABCB1 gene, and one non-functioning gene) are less sensitive to acepromazine than dogs which are homozygous (that is, which have two copies of the mutant gene). 75% of Collies carry the mutated ABCB1 gene, as do 50% of Australian Shepherds. Other affected breeds include: Border Collie, English Shepherd, German Shepherd, Old English Sheepdog, and Sighthounds, shelties, long haired greyhound. [21]

Tests for this mutation are available. [22]

Equine

In equine surgery, premedication with acepromazine has been shown to reduce the perianaesthetic mortality rate, possibly due to its actions as a sedative and anxiolytic. [5] It is less effective as a sedative if the horse is already excited. [23]

Additionally, acepromazine is used as a vasodilator in the treatment of laminitis, 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 experiencing equine exertional rhabdomyolysis. [7]

Acepromazine should not be used in horses intended for human consumption. [24]

Adverse effects

Side effects are not common, but the use of acepromazine in stallions should be used with caution (but is not absolutely contraindicated) due to the risk of paraphimosis and priapism. [6]

Acepromazine also lowers blood pressure, and should therefore be used with caution in horses that are experiencing anemia, dehydration, shock, or colic. It should not be used in horses dewormed with piperazine. [23]

Related Research Articles

<span class="mw-page-title-main">Chlorpromazine</span> Antipsychotic medication

Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar disorder, severe behavioral problems in children including those with attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given orally, by intramuscular injection, or intravenously.

<span class="mw-page-title-main">Perphenazine</span> Antipsychotic medication

Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades.

<span class="mw-page-title-main">Promethazine</span> Pharmaceutical drug

Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people who are agitated or anxious, an effect that has led to some recreational use. Promethazine is taken by mouth (oral), as a rectal suppository, or by injection into a muscle (IM).

<span class="mw-page-title-main">Prochlorperazine</span> Medication for nausea, psychosis, and anxiety

Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.

<span class="mw-page-title-main">Levomepromazine</span> Typical antipsychotic medication

Levomepromazine, also known as methotrimeprazine, is a phenothiazine neuroleptic drug. Brand names include Nozinan, Levoprome, Detenler, Hirnamin, Levotomin and Neurocil. It is a low-potency antipsychotic with strong analgesic, hypnotic and antiemetic properties that are primarily used in palliative care.

<span class="mw-page-title-main">Xylazine</span> Veterinary anesthetic, sedative and analgesic

Xylazine is a structural analog of clonidine and an alpha-2 adrenergic receptor agonist, sold under many trade names worldwide, most notably the Bayer brand name Rompun, as well as Anased, Sedazine and Chanazine.

<span class="mw-page-title-main">Chlorprothixene</span> Typical antipsychotic medication

Chlorprothixene, sold under the brand name Truxal among others, is a typical antipsychotic of the thioxanthene group.

<span class="mw-page-title-main">Droperidol</span> Antidopaminergic drug

Droperidol is an antidopaminergic drug used as an antiemetic and as an antipsychotic. Droperidol is also often used as a rapid sedative in intensive-care treatment, and where "agitation aggression or violent behavior" are present.

<span class="mw-page-title-main">Butorphanol</span> Opioid analgesic

Butorphanol is a morphinan-type synthetic agonist–antagonist opioid analgesic developed by Bristol-Myers. Butorphanol is most closely structurally related to levorphanol. Butorphanol is available as the tartrate salt in injectable, tablet, and intranasal spray formulations. The tablet form is only used in dogs, cats and horses due to low bioavailability in humans.

<span class="mw-page-title-main">Cyproheptadine</span> Antihistamine medication

Cyproheptadine, sold under the brand name Periactin among others, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.

<span class="mw-page-title-main">Propiomazine</span> Chemical compound

Propiomazine, sold under the brand name Propavan among others, is an antihistamine which is used to treat insomnia and to produce sedation and relieve anxiety before or during surgery or other procedures and in combination with analgesics as well as during labor. Propiomazine is a phenothiazine, but is not used therapeutically as a neuroleptic because it does not block dopamine receptors well.

<span class="mw-page-title-main">Promazine</span> Chemical compound

Promazine, is used as a short-term add-on treatment for psychomotor agitation. Its approved uses in people is limited, but is used as a tranquilizer in veterinary medicine. It has weak antipsychotic effects but is generally not used to treat psychoses.

<span class="mw-page-title-main">Dexmedetomidine</span> Anxiolytic, sedative, and pain medication

Dexmedetomidine, sold under the trade name Precedex among others, is a drug used in humans for sedation. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It is also used in humans to treat acute agitation associated with schizophrenia or bipolar I or II disorder.

<span class="mw-page-title-main">Azaperone</span> Chemical compound

Azaperone is a pyridinylpiperazine and butyrophenone neuroleptic drug with sedative and antiemetic effects, which is used mainly as a tranquilizer in veterinary medicine. It is uncommonly used in humans as an antipsychotic drug.

<span class="mw-page-title-main">Detomidine</span> Chemical compound

Detomidine is an imidazole derivative and α2-adrenergic agonist, used as a large animal sedative, primarily used in horses. It is usually available as the salt detomidine hydrochloride. It is a prescription medication available to veterinarians sold under various trade names.

Veterinary anesthesia is a specialization in the veterinary medicine field dedicated to the proper administration of anesthetic agents to non-human animals to control their consciousness during procedures. A veterinarian or a Registered Veterinary Technician administers these drugs to minimize stress, destructive behavior, and the threat of injury to both the patient and the doctor. The duration of the anesthesia process goes from the time before an animal leaves for the visit to the time after the animal reaches home after the visit, meaning it includes care from both the owner and the veterinary staff. Generally, anesthesia is used for a wider range of circumstances in animals than in people not only due to their inability to cooperate with certain diagnostic or therapeutic procedures, but also due to their species, breed, size, and corresponding anatomy. Veterinary anesthesia includes anesthesia of the major species: dogs, cats, horses, cattle, sheep, goats, and pigs, as well as all other animals requiring veterinary care such as birds, pocket pets, and wildlife.

<span class="mw-page-title-main">Maropitant</span> Veterinary medication

Maropitant (INN; brand name: Cerenia, used as maropitant citrate (USAN), is a neurokinin-1 (NK1) receptor antagonist developed by Zoetis specifically for the treatment of motion sickness and vomiting in dogs. It was approved by the FDA in 2007, for use in dogs and in 2012, for cats.

<span class="mw-page-title-main">Atipamezole</span> Veterinary drug

Atipamezole, is a synthetic α2 adrenergic receptor antagonist indicated for the reversal of the sedative and analgesic effects of dexmedetomidine and medetomidine in dogs. Its reversal effect works by competing with the sedative for α2-adrenergic receptors and displacing them. It is mainly used in veterinary medicine, and while it is only licensed for dogs and for intramuscular use, it has been used intravenously, as well as in cats and other animals(intravenous use in cats and dogs is not recommended due to the potential for cardiovascular collapse. This occurs due to profound hypotension caused by reversal of the alpha 1 effects while the reflex bradycardia is still in effect.). There is a low rate of side effects, largely due to atipamezole's high specificity for the α2-adrenergic receptor. Atipamezole has a very quick onset, usually waking an animal up within 5 to 10 minutes.

Barbiturate dependence develops with regular use of barbiturates. This in turn may lead to a need for increasing doses of the drug to get the original desired pharmacological or therapeutic effect. Barbiturate use can lead to both addiction and physical dependence, and as such they have a high potential for excess or non-medical use, however, it does not affect all users. Management of barbiturate dependence involves considering the affected person's age, comorbidity and the pharmacological pathways of barbiturates.

References

  1. ↑ "Acepromazine Maleate Injection for Animal Use". Drugs.com. Retrieved 2017-06-11.
  2. ↑ "Acepromazine: Pet Anxiety Medication for Dogs & Cats". 1800PetMeds. Retrieved 2017-06-11.
  3. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-03.
  4. ↑ Collard JF, Maggs R (June 1958). "Clinical trial of acepromazine maleate in chronic schizophrenia". British Medical Journal. 1 (5085): 1452–1454. doi:10.1136/bmj.1.5085.1452. PMC   2029326 . PMID   13536530.
  5. 1 2 Dugdale 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. PMID   26970940.
  6. 1 2 Plumb DC (2011). Plumb's Veterinary Drug Handbook, 7th ed. Ames, Iowa: Wiley-Blackwell. pp. 4–5. ISBN   978-0-4709-5965-7.
  7. 1 2 Forney B. "Acepromazine Maleate for Veterinary Use". Wedgewood pharmacy. Retrieved 2017-06-10.
  8. 1 2 Choudhary G. "Determination of Acepromazine and its Major Metabolite in Equine Serum by LC-MS/MS using the Finnigan LCQ Deca XP Plus Ion Trap Mass Spectrometer" (PDF). Thermo Electron Corporation.
  9. 1 2 3 Maddison JE, Page SW, Church D, eds. (2008). Small Animal Clinical Pharmacology (2 ed.). Edinburgh; New York: Saunders/Elsevier. ISBN   9780702028588.
  10. ↑ 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. PMID   28404438.
  11. ↑ Kolahian S (2014). "Efficacy of Different Antiemetics with Different Mechanism of Action on Xylazine Induced Emesis in Cats" (PDF). Iranian Journal of Veterinary Surgery. 9 (1): 10.
  12. ↑ Park E. Motion sickness. In: General Medical Officer (GMO) Manual: Clinical Section. Wilmette, IL: Brookside Press; 1999.
  13. 1 2 Marroum PJ (1990). Pharmacokinetic studies of acepromazine in the cat and the horse, studies in lipophilicity, red blood cell partitioning and protein binding (PhD). University of Florida.
  14. ↑ Wingfield W, Raffe M (2002-09-29). The Veterinary ICU Book. Teton NewMedia. p. 81. ISBN   9781893441132.
  15. 1 2 Riviere JE, Papich MG, eds. (2009). Veterinary pharmacology and therapeutics (9th ed.). Ames, Iowa: Wiley-Blackwell. pp.  340, 561. ISBN   978-0-8138-2061-3.
  16. 1 2 Brooks W. "Acepromazine (PromAce)". The Pet Pharmacy. Retrieved 2017-06-11.
  17. ↑ 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. PMID   16822767.
  18. ↑ 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.
  19. ↑ Wieder ME, Gray BP, Brown PR, Hudson S, Pearce CM, Paine SW, Hillyer L (2012). "Identification of Acepromazine and Its Metabolites in Horse Plasma and Urine by LC–MS/MS and Accurate Mass Measurement". Chromatographia. 75 (11–12): 635–643. doi:10.1007/s10337-012-2234-4. ISSN   0009-5893. S2CID   97040034.
  20. 1 2 Ettinger SJ, Feldman EC, eds. (2010). Textbook of veterinary internal medicine: Diseases of the dog and the cat (7th ed.). St. Louis, Mo.: Elsevier Saunders. ISBN   978-1-4160-6593-7.
  21. 1 2 3 Mealey 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. PMID   23890239. S2CID   1780375.
  22. ↑ "Multidrug Sensitivity in Dogs". Washington State University.
  23. 1 2 Thayer A (2009). "HA Special Care Drug Chart" (PDF). Retrieved 2017-06-19.
  24. ↑ National Office of Animal Health (2004). NOAH Compendium of Data Sheets for Animal Medicines 2005:38. Enfield: National Office of Animal Health. ISBN   9780954803704.
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