Acepromazine maleate targets dopamine receptors in the central nervous system as an antagonist. It is a phenothiazine antipsychotic drug that blocks dopamine D2 receptors. By antagonizing dopamine receptors, acepromazine maleate causes sedation, muscular relaxation, and a reduction in spontaneous activity. It also has antiemetic effects. The compound's mechanism is similar to other phenothiazine antipsychotics.

In vitro, acepromazine maleate has been characterized as a dopamine receptor antagonist. Its activity at dopamine D2 receptors has been confirmed in receptor binding and functional assays. The compound's ability to block dopamine-mediated signaling contributes to its sedative and antipsychotic effects. The maleate salt form does not significantly alter the pharmacological activity compared to the base compound.

In vivo, acepromazine maleate causes sedation, muscular relaxation, and a reduction in spontaneous activity in animals. It is frequently used in veterinary medicine as a sedative and antiemetic. The drug's sedative effects are mediated through dopamine receptor antagonism in the CNS. It is used to calm anxious or aggressive animals and as a pre-anesthetic agent.

In non-cell-based receptor binding assays, acepromazine maleate's affinity for dopamine receptors is evaluated using radioligand competition binding experiments. Membrane preparations from cells expressing dopamine D2 receptors are incubated with a radiolabeled D2-selective ligand and varying concentrations of acepromazine maleate. After incubation, bound and free radioligand are separated, and radioactivity is measured. Competition curves are generated to determine IC50 and Ki values.

In vitro cellular assays for acepromazine maleate involve measuring its antagonist activity at dopamine receptors in cultured cells. Cells expressing dopamine D2 receptors are treated with acepromazine maleate in the presence of a dopamine agonist, and receptor activation is assessed by measuring downstream signaling such as cAMP accumulation. The compound's ability to inhibit agonist-induced signaling is quantified to confirm its antagonist activity.

In vivo animal studies for acepromazine maleate are conducted primarily in veterinary species. The compound is administered via oral, intramuscular, or intravenous routes, and its sedative and antiemetic effects are assessed. Behavioral observations, physiological measurements, and clinical evaluations are used to assess the drug's efficacy and safety. Acepromazine maleate is frequently used in dogs, cats, and horses.

The biological half-life is 3 hours in horses.
Acepromazine maleate is well absorbed after administration and is distributed throughout the body, including the central nervous system. It is metabolized in the liver and eliminated primarily by renal excretion. The maleate salt form is used to improve the compound's solubility and stability. Detailed pharmacokinetic parameters are available from veterinary pharmacology sources.

The most common side effects of acepromazine maleate include sedation, hypotension, and hypothermia. In animals, it may cause bradycardia, respiratory depression, and, in some cases, extrapyramidal symptoms. Acepromazine maleate should be used with caution in animals with cardiovascular disease, liver disease, or seizure disorders.

[1]. Identification of acepromazine in hair: an illustration of the difficulties encountered in investigating drug-facilitated crimes. J Forensic Sci. 2008;53(3):755-759.

[2]. Effects of xylazine and acepromazine on bronchomotor tone of anaesthetised ponies. Equine Vet J. 1988;20(3):185-188.

[3]. Prevention of sudden cardiac death by the atypical neuroleptic acepromazine following status epilepticus in rats. Life Sci. 1994;54(24):PL457-PL462.

Promethazine belongs to the phenothiazine class of compounds. Its structure is 10H-phenothiazine, with an acetyl group at position 2 and a 3-(dimethylamino)propyl group at position 10. It is a phenothiazine antipsychotic drug. Promethazine is a methyl ketone, aromatic ketone, tertiary amine compound belonging to the phenothiazine class. Promethazine is a phenothiazine derivative psychotropic drug, rarely used in humans, but commonly used as a sedative and antiemetic in animals. Promethazine is a phenothiazine derivative with inhibitory effects on the central nervous system. Promethazine acts as a dopamine receptor antagonist in the central nervous system, causing sedation, muscle relaxation, and reduced spontaneous activity. Its rapid onset of action and low toxicity are of particular value in veterinary medicine. A phenothiazine drug used to treat psychosis. See also: Promethazine maleate (in salt form).

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Drug Indications
Promethazine was first used in humans in the 1950s as an antipsychotic drug. It is now rarely used in humans. Promethazine is commonly used in animals as a sedative and antiemetic. Its main value lies in calming and sedating anxious animals.

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Mechanism of Action
Promethazine acts as an antagonist (blocker) on different postsynaptic receptors—dopaminergic receptors (D1, D2, D3, and D4 subtypes—with different antipsychotic properties for productive and nonproductive symptoms), serotonergic receptors (5-HT1 and 5-HT2, with anti-anxiety, antidepressant, and anti-aggressive effects, and can reduce the side effects of extrapyramidal drugs, but can also cause weight gain, hypotension, sedation, and ejaculatory dysfunction), histaminergic receptors (H1 receptors, with sedative, antiemetic, dizziness, hypotension, and weight gain effects), and α1/α2 receptors (with antisympathetic effects, can lower blood pressure, and inhibit reflexes). Tachycardia, dizziness, sedation, excessive salivation and urinary incontinence, and sexual dysfunction (but may also alleviate pseudo-Parkinsonian syndrome—this is controversial). Finally, it acts on muscarinic (cholinergic) M1/M2 receptors (causing anticholinergic symptoms such as dry mouth, blurred vision, constipation, difficulty/inability to urinate, sinus tachycardia, ECG changes, and memory loss, but the anticholinergic effect may reduce extrapyramidal side effects).

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Pharmacodynamics
Acetrazine is a phenothiazine psychotropic drug. Acetrazine acts on various levels of the central nervous system—primarily the subcortical level—and multiple organ systems. Acetrazine has potent antiadrenergic activity and weak peripheral anticholinergic activity; its ganglion blocking effect is relatively weak. It also has mild antihistamine and antiserotonin activity.
Acepromazine maleate is the maleate salt form of acepromazine, a phenothiazine derivative used primarily in veterinary medicine as a sedative and antiemetic. It acts as a dopamine receptor antagonist in the CNS, causing sedation, muscular relaxation, and reduced spontaneous activity. Acepromazine maleate is available under various brand names including Calmivet and Vetranquil. It is not commonly used in human medicine.

C23H26N2O5S

442.53

442.156

3598-37-6

Acepromazine;61-00-7

6077

Light yellow to yellow solid powder

1.155g/cm3

497ºC at 760 mmHg

135-136ºC

254.4ºC

4.22

0

4

5

23

414

0

CC(C(C=C1N2CCCN(C)C)=CC=C1SC3=C2C=CC=C3)=O.O=C(O)/C=C\C(O)=O

FQRHOOHLUYHMGG-BTJKTKAUSA-N

InChI=1S/C19H22N2OS.C4H4O4/c1-14(22)15-9-10-19-17(13-15)21(12-6-11-20(2)3)16-7-4-5-8-18(16)23-195-3(6)1-2-4(7)8/h4-5,7-10,13H,6,11-12H2,1-3H31-2H,(H,5,6)(H,7,8)/b2-1-

1-(10-(3-(dimethylamino)propyl)-10H-phenothiazin-2-yl)ethan-1-one maleate

AcepromazineAcepromazine maleate Sch 10649 Sch10649Sch-10649

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~100 mg/mL (~226.0 mM; with ultrasonication)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.65 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.65 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)