Atipamezole

Source: Wikipedia, the free encyclopedia.

Atipamezole
Clinical data
Trade namesAntisedan, others
AHFS/Drugs.com
License data
Reversal agent
ATCvet code
Legal status
Legal status
Pharmacokinetic data
MetabolismLiver
Onset of actionLess than 3 min.
Elimination half-life2.6 hours (dogs)
ExcretionKidney
Identifiers
  • 4-(2-Ethyl-1,3-dihydroinden-2-yl)-3H-imidazole
JSmol)
  • [nH]1cc(nc1)C3(Cc2c(cccc2)C3)CC
  • InChI=1S/C14H16N2/c1-2-14(13-9-15-10-16-13)7-11-5-3-4-6-12(11)8-14/h3-6,9-10H,2,7-8H2,1H3,(H,15,16) checkY
  • Key:HSWPZIDYAHLZDD-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Atipamezole , sold under the brand name Antisedan among others, is a synthetic

cats and other animals(intravenous use in cats and dogs is not recommended due to the potential for cardiovascular collapse. This occurs due to profound hypotension caused by reversal of the alpha 1 effects while the reflex bradycardia is still in effect.). There is a low rate of side effects, largely due to atipamezole's high specificity for the α2-adrenergic receptor. Atipamezole has a very quick onset, usually waking an animal up within 5 to 10 minutes.[medical citation needed
]

It was originally released in 1996.

generic medication.[8]

Medical uses

Atipamezole is a veterinary drug whose prime purpose is to reverse the effects of the sedative

cardiovascular depression that dexmedetomidine causes.[9][12][13]

Atipamezole is licensed in the United States for

intranasally.[17][18]

Atipamezole has also been used as an antidote for various toxicities in dogs. For example, the anti-

decongestants such as ephedrine and pseudoephedrine.[22]

Available forms

Atipamezole is sold at 5 mg/mL for ease of use: 5 times as much atipamezole as medetomidine is needed for full reversal, and because medetomidine is sold as 1 mg/mL, 1 mL of atipamezole reverses 1 mL of medetomidine.[23] When the enantiomerically pure version of medetomidine (dexmedetomidine) was released, it was sold at 0.5 mg/mL, because it was twice as strong as medetomidine. As such, 1 mL of atipamezole also reverses 1 mL of dexmedetomidine.[10][12]

Specific populations

Atipamezole is not recommended for animals that are pregnant,

lactating, or slated for breeding.[24]

Contraindications

While there are no absolute contraindications to atipamezole, it is recommended against being given with

telazol(tiletamine); because it reverses only the dexmedetomidine, the ketamine or telazol will still be active, and the animal can wake up excited, delirious, and with muscle contractions.[25] Some recommend not using it in dogs sedated with ketamine at all, since they can convulse due to the excitement effect.[26]

Side effects

Atipamezole's low rate of side effects is due to its high specificity for

dopamine receptors.[12][27][28] There is occasional vomiting, hypersalivation, and diarrhea. It can potentially cause CNS excitement, which can lead to tremors, tachycardia (increased heart rate), and vasodilation. The vasodilation leads to a transient decrease in blood pressure, which (in dogs) increases to normal within 10 minutes.[9] There have been reports of transient hypoxemia.[25] The chance of side effect can be minimized by administering atipamezole slowly.[12]

Atipamezole is sold as Antisedan.

There is a possibility of the sedation reversing abruptly, leading to nervous, aggressive, or delirious dogs.[9] Such cases are more associated with intravenous administration[29] (which has a faster onset than IM administration). The rapid administration of atipamezole leads to sudden displacement of dexmedetomidine from peripheral ɑ2-adrenergic receptors; this can cause a sudden drop in blood pressure, which is followed by a reflex tachycardia and hypertension.[12][26][30]

There have been some cases where intravenous administration of atipamezole lead to death via

cardiovascular collapse. This is thought to be combination of sudden hypotension added onto the low heart rate caused by sedatives.[12]

There is some possibility of the animal relapsing into sedation after being given atipamezole, made more likely if the original sedative was given intravenously.[9]

Rats and monkeys have experienced increased sexual activity after being given atipamezole.[31][32]

Overdose

The

creatinine kinase, aspartate transaminase, and alanine transaminase. Dogs who received atipamezole without first receiving dexmedetomidine have shown no clinical signs other than mild muscle tremors.[9][23]

Pharmacology

Mechanism of action

ɑ2-adrenergic receptors agonist. It does not directly interact with dexmedetomidine;[34] rather, their structural similarity allows atipamezole to easily compete for receptor binding sites.[12]

Atipamezole reverses analgesia by blocking norepinephrine feedback inhibition on nociceptors.[12][31]

Site Ki (nM) Species Ref
α1 3160 Human [35]
α2A 1.9 Human [36]
α2B 2.2 Human [36]
α2C 4.2 Human [36]
The Ki refers to a drug's affinity for a receptor. The smaller

the Ki, the higher the affinity for that receptor.

Pharmacokinetics

Out of the three ɑ2-antagonists commonly used in veterinary medicine (atipamezole, yohimbine, and tolazine), atipamezole shows the highest preference for ɑ2- over ɑ1-receptors, binding to them with a ratio of 8526:1.[12] It shows no preference for a particular ɑ2-receptor subtype.[31]

Atipamezole has a rapid onset: it reverses the decreased heart rate caused by sedation within three minutes. The animal usually begins waking up within 5–10 minutes. In a study of over 100 dogs, more than half could stand up within 5 minutes, and 96% could stand up within 15. Atipamezole reaches maximum serum concentration within 10 minutes of IM administration.[9] Atipamezole is distributed extensively to the tissues; at a particular time, concentrations in the brain reach two to three times the concentration in the plasma.[27]

Atipamezole undergoes heavy

first-pass metabolism in the liver,[27] which includes the glucuronidation at nitrogen during.[37] Metabolites are mostly excreted in the urine.[38]

The elimination half-life is 2.6 hours in dogs and 1.3 hours rats.[9][20]

Research

Atipamezole's effects on

cognitive function have been studied in rats and in humans. While low doses in rats improved alertness, selective attention, learning, and recall, higher doses generally impaired cognitive function (most likely due to norepinephrine overactivity).[31] In rats, it has also been shown to improve cognitive function decreased by strokes or brain lesions.[20] Studies in humans have found it to increase focus but decrease multitasking abilities.[27] Atipamezole has also been researched in humans as a potential anti-Parkinsonian.[27]

Because atipamezole increases sexual activity in monkeys, there have been claims of its potential to treat erectile dysfunction.[32]

Notes

  1. ^ Because dexmedetomidine is the only pharmacologically active component of medetomidine, they will both be referred to as dexmedetomidine from here on out.

References

  1. ^ "Antisedan Product information". health-products.canada.ca. 24 March 2011. Retrieved 5 April 2024.
  2. ^ "Antisedan- atipamezole hydrochloride injection, solution". DailyMed. 18 June 2020. Retrieved 5 April 2024.
  3. ^ "Contrased- atipamezole hydrochloride injection, solution". DailyMed. 1 March 2024. Retrieved 5 April 2024.
  4. ^ "Cropamezole- atipamezole hydrochloride injection, solution". DailyMed. 26 December 2023. Retrieved 5 April 2024.
  5. ^ "Revertased- atipamezole hydrochloride injection, solution". DailyMed. 14 September 2023. Retrieved 5 April 2024.
  6. ^ "Revertidine- atipamezole hydrochloride injection, solution". DailyMed. 12 January 2023. Retrieved 5 April 2024.
  7. ISBN 978-1-4377-0282-8
    .
  8. ^ "Atipamezole". Drugs.com. Retrieved 7 August 2019.
  9. ^ a b c d e f g h i "Antisedan for Animal Use". Drugs.com. Retrieved 24 February 2018.
  10. ^ a b Cote 2010, p. 1623.
  11. ^
    ISBN 978-1-4377-0192-0
    .
  12. ^
    ISBN 978-0-8138-2061-3
    .
  13. ISSN 0003-2999
    .
  14. PMID 15516790
    .
  15. S2CID 25527884
    .
  16. ISBN 978-1-4557-7399-2
    .
  17. ISBN 978-0-323-24293-6
    .
  18. ISBN 978-1-4200-0952-1
    .
  19. ISBN 978-0-12-370467-2
    .
  20. ^ a b c d Bahri L (May 2008). "Pharm Profile: Atipamezole". Compendium. 30 (5).
  21. ISBN 978-0-12-370467-2
    .
  22. ^ Cote 2010, pp. 126, 285.
  23. ^
    ISBN 978-0-7020-5423-5.{{cite book}}: CS1 maint: DOI inactive as of January 2024 (link
    )
  24. ISBN 978-0-16-072065-9
    .
  25. ^
    ISBN 978-1-4377-1448-7
    .
  26. ^
    ISBN 978-1-118-27933-5
    .
  27. ^
    PMID 16389294
    .
  28. ISBN 978-1-59161-034-2
    .
  29. ^ Fish 2008, p. 371.
  30. ISBN 978-1-4160-6477-0
    .
  31. ^ a b c d Fish 2008, pp. 53–54.
  32. ^
    ISBN 978-0-08-058378-5
    .
  33. ^ "Safety Data Sheet" (PDF). Zoetis. 20 March 2017.
  34. ISBN 978-0-7506-8812-3
    .
  35. PMID 1656026
    .
  36. ^
    PMID 20809632
    .
  37. PMID 11854148
    .
  38. ISBN 978-1-4377-0195-1
    .

Further reading

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Atipamezole&oldid=1217329427"