1649-18-9 Usage
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
Different sources of media describe the Uses of 1649-18-9 differently. You can refer to the following data:
1. Sedative; tranquilizer.
2. 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.
Check Digit Verification of cas no
The CAS Registry Mumber 1649-18-9 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 1,6,4 and 9 respectively; the second part has 2 digits, 1 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1649-18:
(6*1)+(5*6)+(4*4)+(3*9)+(2*1)+(1*8)=89
89 % 10 = 9
So 1649-18-9 is a valid CAS Registry Number.
InChI:InChI=1/C19H22FN3O/c20-17-8-6-16(7-9-17)18(24)4-3-11-22-12-14-23(15-13-22)19-5-1-2-10-21-19/h1-2,5-10H,3-4,11-15H2
1649-18-9Relevant articles and documents
Evaluation of the effects of the enantiomers of reduced haloperidol, azaperol, and related 4-amino-1-arylbutanols on dopamine and σ receptors
Jaen,Caprathe,Pugsley,Wise,Akunne
, p. 3929 - 3936 (1993)
The enantiomers of reduced haloperidol (3a), azaperol (3b), and the related compound BMY-14802 (3c) were prepared in high optical purity. The affinity of these compounds for dopamine D2 and D3 receptors, and σ S1 and S2 sites was determined in vitro. Both enantiomers of 3a display greatly decreased affinity for D2 and D3 receptors compared to haloperidol, although they still possess affinities in the 100-200-nM range. Both enantiomers of 3a possess potent and equal affinity for S1 sites (K(i): 1-2 nM), only slightly weaker than haloperidol (K(i): 0.33 nM). At S2 sites, (R)-(+)-3a displays similar affinity to haloperidol (K(i): 31 and 26 nM, respectively), while (S)-(-)-3a is slight more potent (K(i): 8.2 nM). The stereoselectivity profile of the enantiomers of 3b at D2 and D3 receptors is quite similar to that of 3a, (S)-(-)-3b being about 4 times more potent than its enantiomer at both receptors. (R)-(+)-3b binds preferentially to σ S1 over S2 sites, while (S)-(-)-3b displays the opposite selectivity profile. Both enantiomers of 3c possess very weak affinity for D2 and D3 receptors. In a manner similar to the enantiomers of 3b, the affinity of (R)-(+)-3c is greater for S1 than S2 sites, while (S)-(-)-3c displays the opposite selectivity profile. Following parenteral administration of both enantiomers of 3a, dopamine synthesis and turnover in rat striatum, cortex, and mesolimbic areas were increased, in a manner similar to the effects produced by haloperidol itself. Additional studies will be required to assess with certainty whether the effects were due to the compounds themselves or simply were a consequence of the in vivo oxidation to haloperidol.
1-aryl-3-(4-pyridine-2-ylpiperazin-1-yl)propan-1-one oximes as potent dopamine D4 receptor agonists for the treatment of erectile dysfunction
Kolasa, Teodozyj,Matulenko, Mark A.,Hakeem, Ahmed A.,Patel, Meena V.,Mortell, Kathleen,Bhatia, Pramila,Henry, Rodger,Nakane, Masaki,Hsieh, Gin C.,Terranova, Marc A.,Uchic, Marie E.,Miller, Loan N.,Chang, Renje,Donnelly-Roberts, Diana L.,Namovic, Marian T.,Hollingsworth, Peter R.,Martino, Brenda,El Kouhen, Odile,Marsh, Kennan C.,Wetter, Jill M.,Moreland, Robert B.,Brioni, Jorge D.,Stewart, Andrew O.
, p. 5093 - 5109 (2007/10/03)
A new series of dopamine D4 receptor agonists, 1-aryl-3-(4-pyridinepiperazin-1-yl)propanone oximes, was designed through the modification of known dopamine D4 receptor agonist PD 168077. Replacement of the amide group with a methylene-oxime moiety produced compounds with improved stability and efficacy. Structure-activity relationsips (SAR) of the aromatic ring linked to the N-4-piperazine ring confirmed the superiority of 2-pyridine as a core for D4 agonist activity. A two-methylene linker between the oxime group and the N-1-piperazine ring displayed the best profile. New dopamine D4 receptor agonists, exemplified by (E)-1-(4-chlorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl)propan-1-one O-methyloxime (59a) and (E)-1-(3-chloro-4-fluorophenyl)-3-(4-pyridin-2- ylpiperazin-1-yl)propan-1-one O-methyloxime (64a), exhibited favorable pharmacokinetic profiles and showed oral bioavailability in rat and dog. Subsequent evaluation of 59a in the rat penile erection model revealed in vivo activity, comparable in efficacy to apomorphine. Our results suggest that the oximes provide a novel structural linker for 4-arylpiperazine-based D 4 agonists, possessing leadlike quality and with potential to develop a new class of potent and selective dopamine D4 receptor agonists.
