Acepromazine Maleate


Chemical Compound: 2-Acetyl-10-(3-dimethylaminopropyl) phenothiazine hydrogen maleate

DEA Classification: Not a controlled substance

Preparations: Generally available in 5-, 10-, 25-mg tablets and 10 mg/ml injectable forms

Clinical Pharmacology

Acepromazine is a low-potency phenothiazine neuroleptic agent that blocks postsynaptic dopamine receptors and increases the turnover rate of dopamine. Acepromazine has a depressant effect on the central nervous system (CNS) resulting in sedation, muscle relaxation, and a reduction in spontaneous activity. In addition, there are anti-cholinergic, antihistaminic, and alpha-adrenergic blocking effects.

Acepromazine, like other phenothiazine derivatives, is metabolized in the liver. Both conjugated and unconjugated metabolites are excreted in urine. Metabolites can be found in the urine of horses up to 96 hours after dosing. Horses should not be ridden within 36 hours of treatment.


Acepromazine is indicated as a preanesthetic agent, for control of intractable animals, as an antiemetic agent to control vomiting due to motion sickness in dogs and cats, and as a tranquilizer in horses.


Acepromazine can produce prolonged depression when given in excessive amounts or when given to animals that are sensitive to the drug. The effects of acepromazine may be additive when used in combination with other tranquilizers and will potentiate general anesthesia. Tranquilizers should be administered in smaller doses during general anesthesia and to animals that are debilitated, animals with cardiac disease, or animals with sympathetic blockage, hypovolemia, or shock. Phenothiazines should be used with caution during epidural anesthetic procedures because they may potentiate the hypotensive effects of local anesthetics. Phenothiazines should not be used prior to myelography.

Acepromazine should not be used in patients with a history of seizures and should be used with caution in young or debilitated animals, geriatric patients, pregnant females, giant breeds, greyhounds, and boxers. Studies in rodents have demonstrated the potential for embryotoxicity. Phenothiazines should not be used in patients with bone marrow depression.

Side Effects

Phenothiazines depress the reticular activating system and brain regions that control vasomotor tone, basal metabolic rate, and hormonal balance. They also affect extrapyramidal motor pathways and can produce muscle tremors and akathisia (restlessness, pacing, and agitation).

Cardiovascular side effects include hypotension, bradycardia, cardiovascular collapse, and reflex tachycardia. Hypertension is possible with chronic use. Syncope, collapse, apnea, and unconsciousness have been reported. Other side effects include hypothermia, ataxia, hyperglycemia, excessive sedation, and aggression. Paradoxical excitability has been reported in horses, cats, and dogs.

Hematological disorders have been reported in human patients taking phenothiazines, including agranulocytosis, eosinophilia, leukopenia, hemolytic anemia, thrombocytopenia, and pancytopenia.

There is anecdotal evidence that chronic use may result in exacerbation of noise-related phobias. Startle reactions to noise can increase with acepromazine use. Acepromazine is contraindicated in aggressive dogs, because it has been reported to facilitate acute aggressiveness in rare cases.

Priapism, or penile prolapse, may occur in male large animals. Acepromazine should be used with caution in stallions, as permanent paralysis of the retractor muscle is possible.

In a safety study, no adverse reactions to acepromazine occurred when it was administered to dogs at three times the upper limit of the recommended daily dosage (1.5 mg/lb). This dose caused mild depression that resolved within 24 hours after termination of dosing. The LD50 (the dose that kills half of the animals [mice] tested) is 61 mg/kg for intravenous administration and 257 mg/kg for oral administration.

Adverse Drug Interactions

Additive depressant effects can occur if acepromazine is used in combination with anesthetics, barbiturates, and narcotic agents. Concurrent use of propranolol can increase blood levels of both drugs. Concurrent use of thiazide diuretics may potentiate hypotension.


Gradually increasing doses of up to 220 mg/kg PO were not fatal in dogs, but resulted in pulmonary edema. Hypotension can occur after rapid intravenous injection causing cardiovascular collapse. Epinephrine is contraindicated for the treatment of acute hypotension produced by phenothiazine tranquilizers because further depression of blood pressure can occur.

Overdosage of phenothiazine antipsychotics in human patients is characterized by severe CNS depression, coma, hypotension, extrapyramidal symptoms, agitation, convulsions, fever, dry mouth, ileus, and cardiac arrhythmias. Treatment is supportive and symptomatic, and it may include gastric lavage, airway support, and cardiovascular support.

Doses in Nonhuman Animals

Dosages should be individualized depending upon the degree of tranquilization required. Generally, as the weight of the animals increases, the dosage requirement in terms of milligram of medication per kilogram weight of the animal decreases. Doses that are 10 times lower than the manufacturer’s recommended dose may be effective. Arousal is most likely in the first 30 minutes after dosing. Maximal effects are generally reached in 15-60 minutes, and the duration of effect is approximately 3-7 hours. There may be large individual variation in response (Tables Doses for antipsychotics for dogs and cats and Doses of antipsychotics for horses).

Table Doses for antipsychotics for dogs and cats

Drug Canine Feline
Acepromazine 0.5-2.0 mg/kg PO q8h or prn 1.0-2.0 mg/kg PO prn
Chlorpromazine 0.8-3.3 mg/kg PO q6h 3.0-6.0 mg/kg PO
Promazine 2.0-6.0 mg/kg IM or IV q4-6h prn 2.0-4.5 mg/kg IM
Thioridizine 1.0-3.0 mg/kg PO ql2-24h
Haloperidol 0.05-2.0 mg/kg PO ql2h 0.1-1.0 mg/kg PO
Pimozide 0.03-0.3 mg/kg PO
Clozapine 1.0-7.0 mg/kg PO
Sulpiride 5.0-10.0 mg/kg PO

prn, according to need.

Table Doses of antipsychotics for horses

Drug Dose
Acepromazine 0.02-0.1 mg/kg IM
Promazine 0.4-1.0 mg/kg IV or 1.0-2.0 mg/kg PO q4-6h
Haloperidol decanoate 0.004 mg/kg IM


Effects Documented in Nonhuman Animals

Several incidences of idiosyncratic aggression in dogs and cats treated with acepromazine have been reported. In an incident report received by the United States Pharmacopeia Veterinary Practitioners’ Reporting Program, a German shepherd dog being treated with acepromazine following orthopedic surgery attacked and killed the other dog in the household, with no prior history of aggression. There were two incidences of aggression following acepromazine administration identified by the FDA Adverse Drug Experience Summary between 1987 and 1994. There are reports of aggressive behavior following oral and parenteral administration of acepromazine. While this is a rare side effect, the potential for serious injury should prompt practitioners to educate owners about this possibility and suggest appropriate precautions.

In horses, acepromazine can be detected in the urine for at least 25 hours after injection of 0.1 mg/kg.