Azaperone Chemical Properties

Melting point:

87-89?C

Boiling point:

236°C (rough estimate)

Density 

1.1513 (estimate)

storage temp. 

Sealed in dry,2-8°C

solubility 

DMF: 15 mg/ml; DMSO: 15 mg/ml; Ethanol: 10 mg/ml; PBS (pH 7.2): insol

pka

8.43±0.19(Predicted)

form 

Solid

color 

Light yellow to yellow

InChIKey

XTKDAFGWCDAMPY-UHFFFAOYSA-N

CAS DataBase Reference

1649-18-9(CAS DataBase Reference)

NIST Chemistry Reference

Azaperone(1649-18-9)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22

Safety Statements 

3/14

RIDADR 

UN2811 6.1/PG 3

WGK Germany 

3

RTECS 

EU4550000

HS Code 

29335990

Toxicity

dog,LDLo,oral,> 20mg/kg (20mg/kg),GASTROINTESTINAL: NAUSEA OR VOMITINGBEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE,Arzneimittel-Forschung. Drug Research. Vol. 24, Pg. 1798, 1974.

Azaperone Usage And Synthesis

Description

Azaperone is a sedative used in veterinary medicine to avoid mortality of pigs during transportation. This alternative substance to chlorpromazine is a sensitizer and a photosensitizer.

Chemical Properties

Off-White Solid

Physical properties

A butyrophenone neuroleptic, azaperone occurs as a white to yellowish-white macrocrystalline powder with a melting point between 90-95°C. It is practically insoluble in water; 1 gram is soluble in 29 mL of alcohol.
Azaperone may also be known as azaperonum, R-1929, Stresnil®, or Suicalm®.

Originator

Azaperone,Dayang Chemicals Co. Ltd.

Uses

Sedative; tranquilizer.

Uses

H1 antihistamine (nonsedating); leucotriene synthesis blocker

Definition

ChEBI: An N-arylpiperazine that is 2-(piperazin-1-yl)pyridine in which the amino hydrogen is replaced by a 3-(4-fluobenzoyl)propyl group. Used mainly as a tranquiliser for pigs and elephants.

Indications

Azaperone is officially indicated for the "control of aggressiveness when mixing or regrouping weanling or feeder pigs weighing up to 36.4 kg" (Package Insert, Stresnil®—P/M; Mallinckrodt). It is also used clinically as a general tranquilizer for swine, to allow piglets to be accepted by aggressive sows, and as a preoperative agent prior to general anesthesia or cesarean section with local anesthesia.
Azaperone has been used as a neuroleptic in horses, but some horses develop adverse reactions (sweating, muscle tremors, panic reaction, CNS excitement) and IV administration has resulted in significant arterial hypotension. Because of these effects, most clinicians avoid the use of this drug in equines.

Manufacturing Process

A mixture of γ-chloro-4'-fluorobutyrophenone and 1-(2'-pyridyl)piperazine is heated on an oil bath. The mixture is then boiled in diisopropyl ether and the precipitates is collected and boiled with water and benzene. The benzene layer is treated with activated charcoal, added to the ethereal filtrate, and evaporated to give a residue which is taken up in diisopropyl ether. After cooling an oil is precipitated, which after decantation and drying yields 1-[γ- (4'-fluorobenzoyl)propyl]-4-(2'-pyridyl)piperazine.

brand name

Stresnil (Janssen Pharmaceutica, Belgium); Suicalm (Janssen Pharmaceutica, Belgium).

Therapeutic Function

Neuroleptic, Hypnotic

Contact allergens

Azaperone is a sedative used in veterinary medicine to avoid mortality of pigs during transportation. This alternative substance to chlorpromazine is a sensitizer and a photosensitizer.

Pharmacology

The butyrophenones as a class cause tranquilization and sedation (sedation may be less than with the phenothiazines), anti-emetic activity, reduced motor activity, and inhibition of CNS catecholamines (dopamine, norepinephrine). Azaperone appears to have minimal effects on respiration and may inhibit some of the respiratory depressant actions of general anesthetics. A slight reduction of arterial blood pressure has been measured in pigs after IM injections of azaperone, apparently due to slight alpha-adrenergic blockade. Azaperone has been demonstrated to prevent the development of halothane-induced malignant hyperthermia in susceptible pigs. Preliminary studies have suggested that the effects of butyrophenones may be antagonized by 4-aminopyridine.

Pharmacokinetics

Minimal information was located regarding actual pharmacokinetic parameters, but the drug is considered to have a fairly rapid onset of action following IM injections in pigs (5-10 minutes) with a peak effect at approximately 30 minutes post injection. It has a duration of action of 2-3 hours in young pigs and 3-4 hours in older swine. The drug is metabolized in the liver with 13% of it excreted in the feces. At 16 hours post-dose, practically all of the drug is eliminated from the body; however in the UK a 10-day slaughter withdrawal has been assigned.

Side effects

Transient salivation, piling, panting and shivering have been reported in pigs. Pigs should be left undisturbed after injection (for approximately 20 minutes) until the drug's full effects have been expressed; disturbances during this period may trigger excitement.
Azaperone has minimal analgesic effects and is not a substitute for appropriate anesthesia or analgesia. Doses above 1 mg/kg may cause the penis to be extruded in boars.

Safety Profile

Poison by ingestion, intravenous, intraperitoneal, and subcutaneous routes. When heated to decomposition it emits very toxic fumes of Fand NOx.

Veterinary Drugs and Treatments

Azaperone is officially indicated for the “control of aggressiveness when mixing or regrouping weanling or feeder pigs weighing up to 36.4 kg” (Package Insert, Stresnil?—P/M; Mallinckrodt). It is also used clinically as a general tranquilizer for swine, to allow piglets to be accepted by aggressive sows, and as a preoperative agent prior to general anesthesia or cesarean section with local anesthesia.
Azaperone has been used as a neuroleptic in horses, but some horses develop adverse reactions (sweating, muscle tremors, panic reaction, CNS excitement) and IV administration has resulted in significant arterial hypotension. Because of these effects, most clinicians avoid the use of this drug in equines.

Overdosage

Overdoses (>1 mg/kg) in boars may cause penis extrusion leading to damage.

storage

Azaperone should be stored at controlled room temperature (15-25°C) and away from light. Do not store above 25°C. Once the vial is opened it should be used within 28 days. No information was located regarding mixing azaperone with other compounds.

Precautions

When used as directed, the manufacturer reports no contraindications (other than for slaughter withdrawal) for the drug. It should not be given IV as a significant excitatory phase may be seen in pigs. Avoid use in very cold conditions as cardiovascular collapse may occur secondary to peripheral vasodilation.
Do not exceed dosing recommendation in boars as the drug may cause the penis to be extruded.
Because Vietnamese Pot Bellied pigs may have delayed absorption due to sequestration of the drug in body fat, re-dose with extreme caution; deaths have resulted after repeat dosing.

Azaperone(1649-18-9)Related Product Information

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