ACEPROMAZINE MALEATE

Description

Acepromazine is a phenothiazine antipsychotic, analog of chlorpromazine , and a dopamine receptor antagonist. It also binds to muscarinic receptors in rat brain (IC₅₀ = 350 nM) and inhibits contractions of guinea pig ileum induced by acetylcholine (; IC₅₀ = 840 nM). Acepromazine inhibits morphine-induced vomiting in dogs. It also inhibits development of a conditioned avoidance response, unconditioned escape response, and catalepsy in rats (ED₅₀s = 0.98, 3.1, and 17 mg/kg, respectively). Formulations containing acepromazine have been used as tranquilizers and anesthetics premedicant in small and large animal veterinary care.

Chemical Properties

Yellow Crystalline Solid

Originator

Sedaject ,Bayer Korea Co.

Uses

Acepromazine maleate has been used:

• as a component of anesthesia cocktail to test its effects on behavioral changes in rats
• as a component of anesthesia cocktail to study its effects on lung resistance of rats
• as an anti-psychotic pharmaceutical agent to study its cytotoxic effects on malignant glioma in glioblastoma (GBM) cells

Uses

antihistamine

Uses

A tranquilizer

Uses

vitamin D2 analog, blood calcium regulator, therapeutc for chronic hypocalcemia

Manufacturing Process

120 g 3-acetylphenothiazine (0.479 mol) are heated to the boil in 1.2 L xylene and a rapid stream of phosgene then passed in for a period of 12 hours. The solvent is then removed by distillation and the residue taken up in 1 L benzene. The benzene solution is heated to the boil and 112 g of γ- dimethylaminopropyl alcohol (1.09 mol) are added within a period of 15 min and the reaction mixture boiled for a further 2 hours. After cooling, the precipitated hydrochloride of the γ-dimethylaminopropyl alcohol washed with benzene and the combined benzene solutions rapidly washed with water in order to remove excess basic alcohol. The material is dried over potash and the hydrochloride precipitated by means of ethereal hydrochloric acid. The hydrochloride may also be precipitated by passing in gaseous hydrogen chloride. After recrystallisation from isopropanol, 157 g (78% of theory) of γ- dimethylaminopropyl 3-acetylphenothiazine-10-carboxylate are obtained. The hydrochloride melts at 212°C.

Therapeutic Function

Neuroleptic, Antiemetic

Biochem/physiol Actions

Acepromazine is a phenothiazine antipsychotic comonly used as a veterinary drug (horses, dogs and cats). The compound is an analogue antipsychotic drug chlorpromazine (#C8138). The drug is thought to block receptors of dopamine in the brain. Recently it was discover that the compound inhibits ABCG2 transported protein, which overexpression in tumors is associated with drug resistance.

Safety Profile

Poison by ingestion, subcutaneous,and intravenous routes. When heated to decomposition itemits highly toxic fumes of NOx and SOx.

Veterinary Drugs and Treatments

Acepromazine is approved for use in dogs, cats, and horses. Labeled indications for dogs and cats include: “. . . as an aid in controlling intractable animals . . . alleviate itching as a result of skin irritation; as an antiemetic to control vomiting associated with motion sickness” and as a preanesthetic agent. The use of acepromazine as a sedative/tranquilizer in the treatment of adverse behaviors in dogs or cats has largely been supplanted by newer, effective agents that have fewer adverse effects. Its use for sedation during travel is controversial and many no longer recommend drug therapy for this purpose.
In horses, acepromazine is labeled “. . . as an aid in controlling fractious animals,” and in conjunction with local anesthesia for various procedures and treatments. It is also commonly used in horses as a pre-anesthetic agent at very small doses to help control behavior.
Although not approved, it is used as a tranquilizer (see doses) in other species such as swine, cattle, rabbits, sheep and goats. Acepromazine has also been shown to reduce the incidence of halothane- induced malignant hyperthermia in susceptible pigs.