Atipamezole: Difference between revisions

{{Short description|Veterinary medication}}

{{Use dmy dates|date=April 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 458284977

| alt =

| image2 = Atipamezole-3D-balls.png

| alt2 =

<!-- Clinical data -->

| pronounce =

| tradename = Antisedan, others

| Drugs.com = {{ubl| {{drugs.com|vet|antisedan}} | {{drugs.com|vet|ataject-atipamezole-hydrochloride-injection-5-0-mg-ml-can.html}} }}

| MedlinePlus =

| DailyMedID = Atipamezole

| pregnancy_AU_comment =

| routes_of_administration = [[Intramuscular]]

| class= [[Reversal agent]]

<!-- Legal status -->

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment = <ref>{{cite web | title=Antisedan Product information | website=health-products.canada.ca | date=24 March 2011 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=61098 | access-date=5 April 2024}}</ref>

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = <ref>{{cite web | title=Antisedan- atipamezole hydrochloride injection, solution | website=DailyMed | date=18 June 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=403065e1-4c1a-433c-bb1b-6a2951946297 | access-date=5 April 2024}}</ref><ref>{{cite web | title=Contrased- atipamezole hydrochloride injection, solution | website=DailyMed | date=1 March 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e6c1f710-04b5-4515-8971-b60211182041 | access-date=5 April 2024}}</ref><ref>{{cite web | title=Cropamezole- atipamezole hydrochloride injection, solution | website=DailyMed | date=26 December 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=47429f8e-8dfa-4e00-b5ab-fc7c0e31c9eb | access-date=5 April 2024}}</ref><ref>{{cite web | title=Revertased- atipamezole hydrochloride injection, solution | website=DailyMed | date=14 September 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51410acc-da0c-4831-9e4e-01cb98c7b933 | access-date=5 April 2024}}</ref><ref>{{cite web | title=Revertidine- atipamezole hydrochloride injection, solution | website=DailyMed | date=12 January 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=17ee6e77-7996-4c60-8739-22a4b0d2e103 | access-date=5 April 2024}}</ref>

| legal_EU =

| legal_EU_comment =

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->

| bioavailability =

| protein_bound =

| metabolism = [[Liver]]

| metabolites =

| onset = Less than 3 min.

| elimination_half-life = 2.6 hours (dogs)

| duration_of_action =

| excretion = [[Kidney]]

<!-- Identifiers -->

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 104054-27-5

| CAS_supplemental =

| IUPHAR_ligand =

| DrugBank = DB11481

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 64427

| ChEBI =

| ChEMBL =

| NIAID_ChemDB =

| PDB_ligand =

| synonyms =

<!-- Chemical and physical data -->

| IUPAC_name = 4-(2-Ethyl-1,3-dihydroinden-2-yl)-3''H''-imidazole

| SMILES = [nH]1cc(nc1)C3(Cc2c(cccc2)C3)CC

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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)

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = HSWPZIDYAHLZDD-UHFFFAOYSA-N

| density =

| density_notes =

| melting_point =

| melting_high =

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| boiling_point =

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| specific_rotation =

'''Atipamezole''' , sold under the brand name '''Antisedan''' among others, is a synthetic [[Alpha-2 adrenergic receptor|α₂ adrenergic receptor]] [[adrenergic antagonist|antagonist]] used for the reversal of the sedative and analgesic effects of [[dexmedetomidine]] and [[medetomidine]] in dogs. Its reversal effect works by competing with the sedative for [[Α2-adrenergic receptors|α₂-adrenergic receptors]] and displacing them. It is mainly used in veterinary medicine, and while it is only licensed for [[dogs]] and for [[intramuscular]] use, it has been used [[intravenously]], as well as in [[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.{{medcn|date=April 2024}}

It was originally released in 1996.<ref>{{cite book | url=https://books.google.com/books?id=4Qzau1jagOYC&pg=PA61 | title=Textbook of Veterinary Internal Medicine - eBook | vauthors = Ettinger SJ, Feldman EC | publisher=Elsevier Health Sciences | year=2009 | isbn=978-1-4377-0282-8 | edition=7th | pages=61 }}</ref> It is available in as a [[generic medication]].<ref>{{Cite web|url=https://www.drugs.com/international/atipamezole.html|title=Atipamezole|website=Drugs.com|access-date=2019-08-07}}</ref>

== Medical uses ==

Atipamezole is a veterinary drug whose prime purpose is to reverse the effects of the sedative [[dexmedetomidine]] (as well as its [[Racemic mixture|racemic]] mixture, [[medetomidine]]).<ref group="note">Because dexmedetomidine is the only pharmacologically active component of medetomidine, they will both be referred to as ''dexmedetomidine'' from here on out.</ref><ref name="drugs.com">{{cite web | url=https://www.drugs.com/vet/antisedan.html | title=Antisedan for Animal Use | work=Drugs.com | access-date=24 February 2018}}</ref>{{Sfn|Cote|2010|p=[https://books.google.com/books?id=EdpavOFUKTQC&pg=PA1623 1623]}} It can also be used to reverse the related sedative [[xylazine]].<ref name="papich">{{cite book | url=https://books.google.com/books?id=PeJTVfaAiYAC&pg=PA56 | title=Saunders Handbook of Veterinary Drugs – E-Book: Small and Large Animal | vauthors = Papich MG | publisher=Elsevier Health Sciences | year=2010 | isbn=978-1-4377-0192-0 | page=56 }}</ref> While it reverses both the sedative and [[analgesic]] (pain-relieving) effects of dexmedetomidine, atipamezole may not entirely reverse the [[cardiovascular]] depression that dexmedetomidine causes.<ref name="drugs.com" /><ref name="riviere" /><ref>{{cite journal | vauthors = Talke P, Harper D, Traber L, Richardson CR, Traber D | date=February 1999 | title=Reversal of medetomidine induced sedation by atipamezole in sheep: Effects on organ blood | journal=Anesthesia & Analgesia | volume=88 | issue=2S | pages=391S | doi=10.1097/00000539-199902001-00388 | issn=0003-2999 }}</ref>

Atipamezole is licensed in the United States for [[intramuscular injection]] (IM) in [[dogs]]; it is, however, used off-label in [[cats]], [[rabbits]],<ref>{{cite journal | vauthors = Kim MS, Jeong SM, Park JH, Nam TC, Seo KM | title = Reversal of medetomidine-ketamine combination anesthesia in rabbits by atipamezole | journal = Experimental Animals | volume = 53 | issue = 5 | pages = 423–428 | date = October 2004 | pmid = 15516790 | doi = 10.1538/expanim.53.423 | doi-access = free }}</ref> and farm animals such as [[horses]] and [[cows]],<ref name="riviere">{{cite book | url=https://books.google.com/books?id=ievLulSqwBAC&pg=PA352 | title=Veterinary Pharmacology and Therapeutics | vauthors = Riviere JE, Papich MG | publisher=John Wiley & Sons | year=2009 | isbn=978-0-8138-2061-3 | edition=illustrated | pages=352–355 }}</ref> as well as in zoo medicine for [[reptiles]] (including [[tortoises]], [[turtles]], and [[alligators]]), [[armadillos]], [[hippopotamuses]], [[giraffe]]s, [[okapi]], and others.<ref>{{cite journal | vauthors = Heaton-Jones TG, Ko JC, Heaton-Jones DL | title = Evaluation of medetomidine-ketamine anesthesia with atipamezole reversal in American alligators (Alligator mississippiensis) | journal = Journal of Zoo and Wildlife Medicine | volume = 33 | issue = 1 | pages = 36–44 | date = March 2002 | pmid = 12216791 | doi = 10.1638/1042-7260(2002)033[0036:EOMKAW]2.0.CO;2 | s2cid = 25527884 }}</ref><ref>{{cite book | url=https://books.google.com/books?id=llBcBAAAQBAJ&pg=PA29 | title=Fowler's Zoo and Wild Animal Medicine, Volume 8 – E-Book | vauthors = Miller RE, Fowler ME | publisher=Elsevier Health Sciences | year=2014 | isbn=978-1-4557-7399-2 | edition=revised | pages=29, 358, 587, 605 }}</ref> It has been given [[intravenously]] (IV), [[subcutaneously]], [[Intraperitoneal injection|intraperitoneally]] and, in [[red-eared slider]]s, [[intranasally]].<ref>{{cite book | url=https://books.google.com/books?id=2phWAgAAQBAJ&pg=PA143 | title=Current Therapy in Reptile Medicine and Surgery - E-Book | vauthors = Mader DR, Divers SJ | publisher=Elsevier Health Sciences | year=2013 | isbn=978-0-323-24293-6 | pages=143, 387 }}</ref><ref>{{cite book | url=https://books.google.com/books?id=fxTNBQAAQBAJ&pg=PA65 | title=Manual of Stroke Models in Rats | vauthors = Wang-Fischer Y | publisher=CRC Press | year=2008 | isbn=978-1-4200-0952-1 | page=65 }}</ref>

Atipamezole has also been used as an antidote for various toxicities in dogs. For example, the anti-[[tick]] medication [[amitraz]] is commonly ingested by dogs who eat their [[Flea collar|anti-tick collars]].<ref>{{cite book | title=Veterinary Toxicology | vauthors = DeClementi C | publisher=Academic Press | year=2007 | isbn=978-0-12-370467-2 | veditors = Gupta R | location=Oxford | pages=1139–1158 | chapter=Chapter 91: Prevention and treatment of poisoning | doi=10.1016/B978-012370467-2/50188-7 }}</ref> Amitraz works by the same mechanism as dexmedetomidine and is thus easily reversed by atipamezole.<ref name="bahri">{{cite journal | vauthors = Bahri L | date=May 2008 | title=Pharm Profile: Atipamezole | url=http://www.vetfolio.com/pharmacology/pharm-profile-atipamezole | journal=Compendium | volume=30 | issue=5 }}</ref><ref>{{cite book | title=Veterinary Toxicology | vauthors = Gupta RC | publisher=Academic Press | year=2007 | isbn=978-0-12-370467-2 | location=Oxford | pages=514–517 | chapter=Chapter 46: Amitraz | doi=10.1016/B978-012370467-2/50143-7 }}</ref> Atipamezole also reverses the hypotension caused by [[tizanidine]] (a muscle relaxant) toxicity, and relieves toxicity from [[decongestants]] such as [[ephedrine]] and [[pseudoephedrine]].{{Sfn|Cote|2010|p=|pp=[https://books.google.com/books?id=EdpavOFUKTQC&pg=PA126 126], [https://books.google.com/books?id=EdpavOFUKTQC&pg=PA285 285]}}

=== Available forms ===

Atipamezole is sold at 5&nbsp;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&nbsp;mg/mL, 1 mL of atipamezole reverses 1 mL of medetomidine.<ref name="clarke">{{cite book | url=https://books.google.com/books?id=hZh5AAAAQBAJ&pg=PA91 | title=Veterinary Anaesthesia E-Book | vauthors = Clarke KW, Trim CM | publisher=Elsevier Health Sciences | year=2013 | isbn=978-0-7020-5423-5 | edition=11th | page=91 | doi=10.1016/B978 | doi-broken-date=31 January 2024 }}</ref> When the enantiomerically pure version of medetomidine (dexmedetomidine) was released, it was sold at 0.5&nbsp;mg/mL, because it was twice as strong as medetomidine. As such, 1 mL of atipamezole also reverses 1 mL of dexmedetomidine.{{Sfn|Cote|2010|p=[https://books.google.com/books?id=EdpavOFUKTQC&pg=PA1623 1623]}}<ref name="riviere" />

=== Specific populations===

Atipamezole is not recommended for animals that are pregnant, [[lactating]], or slated for breeding.<ref>{{cite book | url=https://books.google.com/books?id=KbCGAAAAMAAJ&pg=PA221 | title=L.S.A., List of C.F.R. Sections Affected | publisher=National Archives of the United States | year=2004 | isbn=978-0-16-072065-9 | page=221 }}</ref>

== Contraindications ==

While there are no absolute contraindications to atipamezole, it is recommended against being given with [[anticholinergics]], as both can cause dramatic increases in heart rate.<ref name="papich" /><ref name="bahri" /> Atipamezole should also not be given too soon after an animal has been given dexmedetomidine mixed with [[ketamine]] or [[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.<ref name="schenk" /> Some recommend not using it in dogs sedated with ketamine at all, since they can convulse due to the excitement effect.<ref name="dugdale" />

== Side effects ==

Atipamezole's low rate of side effects is due to its high specificity for [[Alpha-2 adrenergic receptor|ɑ₂-adrenergic receptors]]; it has very little affinity for [[Alpha-1 adrenergic receptor|ɑ₁-adrenergic receptors]] and no affinity for most [[Serotonin receptor|serotonin]], [[Muscarinic acetylcholine receptor|muscarinic]], and [[dopamine receptors]].<ref name="riviere" /><ref name="pertovaara">{{cite journal | vauthors = Pertovaara A, Haapalinna A, Sirviö J, Virtanen R | title = Pharmacological properties, central nervous system effects, and potential therapeutic applications of atipamezole, a selective alpha2-adrenoceptor antagonist | journal = CNS Drug Reviews | volume = 11 | issue = 3 | pages = 273–288 | date = 1 September 2005 | pmid = 16389294 | pmc = 6741735 | doi = 10.1111/j.1527-3458.2005.tb00047.x | doi-access = free }}</ref><ref>{{cite book | url=https://books.google.com/books?id=gCHlAgAAQBAJ&pg=PA42 | title=The Practice of Veterinary Anesthesia: Small Animals, Birds, Fish and Reptiles | vauthors = Sawyer D | publisher=CRC Press | year=2008 | isbn=978-1-59161-034-2 | series=Manson Series | page=42 }}</ref> There is occasional [[vomiting]], [[hypersalivation]], and [[diarrhea]]. It can potentially cause [[Central nervous system|CNS]] excitement, which can lead to [[tremor]]s, [[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.<ref name="drugs.com" /> There have been reports of transient [[hypoxemia]].<ref name="schenk">{{cite book | url=https://books.google.com/books?id=jz-IkIugVrEC&pg=PA402 | title=Saunders Comprehensive Review of the NAVLE – E-Book | vauthors = Schenck P | publisher=Elsevier Health Sciences | year=2009 | isbn=978-1-4377-1448-7 | page=402 }}</ref> The chance of side effect can be minimized by administering atipamezole slowly.<ref name="riviere" />

[[File:Antisedan bottle.jpg|thumb|Atipamezole is sold as Antisedan.]]

There is a possibility of the sedation reversing abruptly, leading to nervous, aggressive, or delirious dogs.<ref name="drugs.com" /> Such cases are more associated with intravenous administration{{Sfn|Fish|2008|p=[https://books.google.com/books?id=zMfSuAuyKwUC&pg=PA371 371]}} (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.<ref name="riviere" /><ref name="dugdale">{{cite book | url=https://books.google.com/books?id=0_7MRlsNbnoC&pg=PA257 | title=Veterinary Anaesthesia: Principles to Practice | vauthors = Dugdale A | publisher=John Wiley & Sons | year=2011 | isbn=978-1-118-27933-5 | pages=257, 368 }}</ref><ref>{{cite book | url=https://books.google.com/books?id=7Ai4BKhi0VUC&pg=PA444 | title=Reptile Medicine and Surgery - E-Book | vauthors = Divers SJ, Mader DR | publisher=Elsevier Health Sciences | year=2005 | isbn=978-1-4160-6477-0 | edition=2 | page=444 }}</ref>

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.<ref name="riviere" />

There is some possibility of the animal relapsing into sedation after being given atipamezole, made more likely if the original sedative was given intravenously.<ref name="drugs.com" />

Rats and monkeys have experienced increased sexual activity after being given atipamezole.{{Sfn|Fish|2008|p=|pp=[https://books.google.com/books?id=zMfSuAuyKwUC&pg=PA53 53–54]}}<ref name="annual">{{cite book | url=https://books.google.com/books?id=pJ1TIGO9VVYC&pg=PA78 | title=Annual Reports in Medicinal Chemistry | publisher=Academic Press | year=1999 | isbn=978-0-08-058378-5 | volume=34 | page=78 }}</ref>

== Overdose ==

The [[LD50|LD₅₀]] of atipamezole for rats is 44&nbsp;mg/kg when given subcutaneously. The [[minimum lethal dose]] in dogs is over 5&nbsp;mg/m²; dogs have tolerated getting ten times the standard dose.<ref name="drugs.com" /><ref>{{cite web | title=Safety Data Sheet | date=20 March 2017 | url=https://www.zoetisus.com/contact/pages/product_information/msds_pi/msds/antisedan.pdf | publisher=Zoetis}}</ref> Signs of overdose include panting, trembling, vomiting, and diarrhea, as well as increased blood levels of [[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.<ref name="drugs.com" /><ref name="clarke" />

== Pharmacology ==

=== Mechanism of action ===

[[File:Dexmedetomidine vs Atipamezole.svg|thumb|The structures of dexmedetomidine and atipamezole, with the similarities in blue.|300x300px]]Atipamezole is a competitive [[Alpha-adrenergic antagonist|antagonist at ɑ₂-adrenergic receptors]] that competes with dexmedetomidine, an [[Alpha-2 adrenergic receptor agonist|ɑ₂-adrenergic receptors agonist]]''.'' It does not directly interact with dexmedetomidine;<ref>{{cite book | url=https://books.google.com/books?id=shcdNYMJud4C&pg=PA191 | title=Pain Management in Small Animals | vauthors = Grant D | publisher=Elsevier Health Sciences | year=2006 | isbn=978-0-7506-8812-3 | pages=191, 199 }}</ref> rather, their structural similarity allows atipamezole to easily compete for receptor binding sites.<ref name="riviere" />

Atipamezole reverses analgesia by blocking [[norepinephrine]] [[Nociceptor#Pathway|feedback inhibition on nociceptors]].<ref name="riviere" />{{Sfn|Fish|2008|p=|pp=[https://books.google.com/books?id=zMfSuAuyKwUC&pg=PA53 53–54]}}

{| class="wikitable"

!Site

!''K''_i (nM)

!Species

!Ref

|-

|[[Alpha-1 adrenergic receptor|α₁]]

|3160

|Human

|<ref>{{cite journal | vauthors = Blaxall HS, Murphy TJ, Baker JC, Ray C, Bylund DB | title = Characterization of the alpha-2C adrenergic receptor subtype in the opossum kidney and in the OK cell line | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 259 | issue = 1 | pages = 323–329 | date = October 1991 | pmid = 1656026 | url = https://pubmed.ncbi.nlm.nih.gov/1656026/ }}</ref>

|-

|[[Alpha-2A adrenergic receptor|α_2A]]

|1.9

|Human

|<ref name=":0">{{cite journal | vauthors = Vacher B, Funes P, Chopin P, Cussac D, Heusler P, Tourette A, Marien M | title = Rigid analogues of the α2-adrenergic blocker atipamezole: small changes, big consequences | journal = Journal of Medicinal Chemistry | volume = 53 | issue = 19 | pages = 6986–6995 | date = October 2010 | pmid = 20809632 | doi = 10.1021/jm1006269 }}</ref>

|-

|[[Alpha-2B adrenergic receptor|α_2B]]

|2.2

|Human

|<ref name=":0" />

|-

|[[Alpha-2C adrenergic receptor|α_2C]]

|4.2

|Human

|<ref name=":0" />

|-

| colspan="4" |<small>The [[Dissociation constant|K_i]] refers to a drug's affinity for a receptor. The smaller</small>

<small>the K_i, the higher the affinity for that receptor.</small>

|}

=== 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.<ref name="riviere" /> It shows no preference for a particular ɑ₂-receptor subtype.{{Sfn|Fish|2008|p=|pp=[https://books.google.com/books?id=zMfSuAuyKwUC&pg=PA53 53–54]}}

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.<ref name="drugs.com" /> 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.<ref name="pertovaara" />

Atipamezole undergoes heavy [[first-pass metabolism]] in the liver,<ref name="pertovaara" /> which includes the [[glucuronidation]] at nitrogen during.<ref>{{cite journal | vauthors = Kaivosaari S, Salonen JS, Taskinen J | title = N-Glucuronidation of some 4-arylalkyl-1H-imidazoles by rat, dog, and human liver microsomes | journal = Drug Metabolism and Disposition | volume = 30 | issue = 3 | pages = 295–300 | date = March 2002 | pmid = 11854148 | doi = 10.1124/dmd.30.3.295 | doi-access = free }}</ref> Metabolites are mostly excreted in the urine.<ref>{{cite book | url=https://books.google.com/books?id=YrE_pIcmlJcC&pg=PA226 | title=Small Animal Pediatrics – E-Book: The First 12 Months of Life | vauthors = Peterson ME, Kutzler M | publisher=Elsevier Health Sciences | year=2010 | isbn=978-1-4377-0195-1 | page=226 }}</ref>

The elimination half-life is 2.6 hours in dogs and 1.3 hours rats.<ref name="drugs.com" /><ref name="bahri" />

== 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).{{Sfn|Fish|2008|p=|pp=[https://books.google.com/books?id=zMfSuAuyKwUC&pg=PA53 53–54]}} In rats, it has also been shown to improve cognitive function decreased by [[stroke]]s or brain lesions.<ref name="bahri" /> Studies in humans have found it to increase focus but decrease multitasking abilities.<ref name="pertovaara" /> Atipamezole has also been researched in humans as a potential [[Parkinson's disease#Management|anti-Parkinsonian]].<ref name="pertovaara" />

Because atipamezole increases sexual activity in monkeys, there have been claims of its potential to treat erectile dysfunction.<ref name="annual" />

== Notes ==

{{Reflist|group=note}}

== References ==

== Further reading ==

{{refbegin}}

* {{cite book|title=Clinical Veterinary Advisor – E-Book: Dogs and Cats| vauthors = Cote E |publisher=Elsevier Health Sciences|year=2010|isbn=978-0-323-06876-5|edition=2nd, revised}}

* {{cite book|title=Anesthesia and Analgesia in Laboratory Animals| vauthors = Fish RE |publisher=Academic Press|year=2008|isbn=978-0-12-373898-1|series=American College of Laboratory Animal Medicine series}}

{{refend}}

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