Azaperone

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Azaperone
Azaperone.svg
Clinical data
AHFS/Drugs.com International Drug Names
Routes of
administration
IM
ATCvet code
Pharmacokinetic data
Metabolism Hepatic
Elimination half-life 4 hours
Identifiers
  • 1-(4-fluorophenyl)-4-(4-pyridin-2-ylpiperazin-1-yl)butan-1-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.015.197 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H22FN3O
Molar mass 327.403 g·mol−1
3D model (JSmol)
Melting point 90 to 95 °C (194 to 203 °F)
  • Fc1ccc(cc1)C(=O)CCCN3CCN(c2ncccc2)CC3
  • InChI=1S/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 Yes check.svgY
  • Key:XTKDAFGWCDAMPY-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Azaperone is a pyridinylpiperazine and butyrophenone neuroleptic drug with sedative and antiemetic effects, which is used mainly as a tranquilizer in veterinary medicine. [1] It is uncommonly used in humans as an antipsychotic drug.

Contents

Azaperone acts primarily as a dopamine antagonist but also has some antihistaminic and anticholinergic properties as seen with similar drugs such as haloperidol. Azaperone may cause hypotension and while it has minimal effects on respiration in pigs, high doses in humans can cause respiratory depression.

Veterinary use

The most common use for azaperone is in relatively small doses as a "serenic" (to reduce aggression) in farmed pigs, either to stop them fighting or to encourage sows to accept piglets. Higher doses are used for anesthesia in combination with other drugs such as xylazine, tiletamine and zolazepam. Azaperone is also used in combination with strong narcotics such as etorphine or carfentanil for tranquilizing large animals such as elephants. [2] Use in horses is avoided as adverse reactions may occur.

The European Medicines Agency has established a maximum residue limit for azaperone when administered to pigs. [3]

Azaperone (under the brand name Stresnil) was approved for use in pigs in the USA in 1983, under NADA 115-732. [4]

Synthesis

52%: Patent: Improved method: Radiolabelled: Azaperone synthesis.svg
52%: Patent: Improved method: Radiolabelled:

The alkylation of 2-chloropyridine (1) with piperazine gives 1-(pyridin-2-yl)piperazine [67980-77-2] (2). The attachement of the sidechain by reaction with 4-chloro-4'-fluorobutyrophenone [3874-54-2] (3) completed the synthesis of azaperone (4).

See also

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References

  1. Posner LP, Burns P (2013). "Sedative agents: tranquilizers, alpha-2 agonists, and related agents. Veterinary pharmacology and therapeutics. 2009:.". In Riviere JE, Papich MG (eds.). Veterinary Pharmacology and Therapeutics (9th ed.). Somerset: Wiley. pp. 337–380 (366). ISBN   978-1-118-68590-7.
  2. "The Elephant Formulary". Archived from the original on 2012-02-05. Retrieved 2007-04-30.
  3. "Azaperone Summary Report (2)" (PDF). European Medicines Agency. Committee for Veterinary Medicinal Products. November 1997. Retrieved 2017-01-15.
  4. "Rules and Regulations" (PDF). Federal Register. 48 (202): 48229. 18 October 1983. Retrieved 2017-01-15.
  5. Jaen, Juan C.; Caprathe, Bradley W.; Pugsley, Thomas A.; Wise, Lawrence D.; Akunne, Hyacinth (1993). "Evaluation of the effects of the enantiomers of reduced haloperidol, azaperol, and related 4-amino-1-arylbutanols on dopamine and .sigma. receptors". Journal of Medicinal Chemistry. 36 (24): 3929–3936. doi:10.1021/jm00076a022.
  6. Janssen Paul Adriaan Jan, U.S. patent 2,958,694 (1960).
  7. Taghizadeh, M. J., Mohammadnia, M. S., Ghalkhani, M., Sohouli, E. (April 2022). "Improved Method for the Total Synthesis of Azaperone and Investigation of Its Electrochemical Behavior in Aqueous Solution". Chemical Research in Chinese Universities. 38 (2): 546–551. doi:10.1007/s40242-021-1061-2. ISSN   1005-9040. S2CID   235614834.
  8. Soudijn, W.; van Wijngaarden, I. (1968). "A rapid and convenient method for the synthesis of labelled tertiary amines". Journal of Labelled Compounds. 4 (2): 159–163. doi:10.1002/jlcr.2590040209.