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Revision as of 13:39, 23 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456660424 of page Medetomidine for the Chem/Drugbox validation project (updated: 'CAS_number').  Latest revision as of 01:23, 20 December 2024 edit Citation bot (talk | contribs)Bots5,416,884 edits Add: pmid, pages, issue, volume. | Use this bot. Report bugs. | Suggested by Pancho507 | Linked from User:Pancho507/sandbox/1 | #UCB_webform_linked 3557/3849 
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{{Short description|Chemical compound}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{more footnotes|date=January 2016}}
{{Drugbox {{Drugbox
| Verifiedfields = changed | Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 408583997 | verifiedrevid = 462101496
| IUPAC_name = (''RS'')-4--3''H''-imidazole | IUPAC_name = (''RS'')-4--3''H''-imidazole
| image = Medetomidine.svg | image = Medetomidine.svg
| imagename = 1 : 1 mixture (racemate) | chirality = ]
| drug_name = Medetomidine

<!--Clinical data--> <!--Clinical data-->
| tradename = | tradename =
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = Veterinary use only | legal_status = Veterinary use only
| routes_of_administration = | routes_of_administration =


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
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| metabolism = | metabolism =
| elimination_half-life = | elimination_half-life =
| excretion = | excretion =


<!--Identifiers--> <!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = <!-- blanked - oldvalue: 86347-14-0 --> | CAS_number = 86347-14-0
| ATCvet = yes | ATCvet = yes
| ATC_prefix = N05 | ATC_prefix = N05
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| ATC_supplemental = | ATC_supplemental =
| PubChem = 68602 | PubChem = 68602
| DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00633 | DrugBank = DB00633
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 61868 | ChemSpiderID = 61868
| UNII_Ref = {{fdacite|changed|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = MR15E85MQM | UNII = MR15E85MQM
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08165 | KEGG = D08165
| ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 48552 | ChEBI = 48552
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
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| chemical_formula = | chemical_formula =
| C=13 | H=16 | N=2 | C=13 | H=16 | N=2
⚫ | smiles = n1cc(c1)C(c2c(c(ccc2)C)C)C
| molecular_weight = 200.279 g/mol
⚫ | smiles = n1cc(nc1)C(c2c(c(ccc2)C)C)C
| InChI = 1/C13H16N2/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13/h4-8,11H,1-3H3,(H,14,15)
| InChIKey = CUHVIMMYOGQXCV-UHFFFAOYAH
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C13H16N2/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13/h4-8,11H,1-3H3,(H,14,15) | StdInChI = 1S/C13H16N2/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13/h4-8,11H,1-3H3,(H,14,15)
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| StdInChIKey = CUHVIMMYOGQXCV-UHFFFAOYSA-N | StdInChIKey = CUHVIMMYOGQXCV-UHFFFAOYSA-N
}} }}

'''Medetomidine''' is a veterinary ] drug with potent ] effects and emerging illicit drug ].<ref name="de Andrade Horn">{{Cite journal | vauthors=de Andrade Horn P, Berida TI, Parr LC, Bouchard JL, Jayakodiarachchi N, Schultz DC, Lindsley CW, Crowley ML | date=October 2024 | title= Classics in Chemical Neuroscience: Medetomidine | journal=ACS Chem Neurosci | volume=15 | issue=21 | pages=3874–3883 | doi=10.1021/acschemneuro.4c00583| doi-access=free | pmid=39405508 | pmc=11587509 }}</ref>

<!-- Side effects and mechanism -->
It is a ] of two ]s, levomedetomidine and ], the latter being the isomer with the pharmacologic effect as an alpha 2- ]. Effects can be reversed using ].

<!-- History and culture -->
It was developed by ].<ref name=Orion>{{cite web | title = Achievements | work = Orion Corporation | url = http://orion.fi/en/Research-and-developement/Achievements/ | archive-url=https://web.archive.org/web/20130315082255/http://orion.fi/en/Research-and-developement/Achievements/ | archive-date=March 15, 2013 }}</ref> It is approved for dogs in the United States, and distributed in the United States by ] Animal Health and by ] Animal Health in Canada under the product name '''Domitor'''. Starting in 2022 Medetomidine has been detected in the US in samples of illicit drugs and associated with overdoses.

The free base form of medetomidine is sold as an antifouling substance for marine paints.<ref name="selektope">{{cite web |last1=Chaabane |first1=Philip | name-list-style = vanc |title=The Selektope Story |url=https://www.pcimag.com/ext/resources/WhitePapers/2016/The-Selektope-Story-v2.pdf |publisher=PCI Magazine |access-date=12 December 2018}}</ref>

==History==
Medetomidine was developed by ] and launched in 2007.<ref name=Orion/>

==Pharmacology==
Medetomidine is a ] of two optical or ]s, levomedetomidine and ].<ref name="mmwr">{{Cite journal |last=Schwarz |first=Evan S. |date=2024 |title=Notes from the Field: Detection of Medetomidine Among Patients Evaluated in Emergency Departments for Suspected Opioid Overdoses — Missouri, Colorado, and Pennsylvania, September 2020–December 2023 |journal=MMWR. Morbidity and Mortality Weekly Report |language=en-us |volume=73 |issue=30 |pages=672–674 |doi=10.15585/mmwr.mm7330a3 |issn=0149-2195|doi-access=free |pmid=39088371 |pmc=11305408 }}</ref> The latter causes the alpha 2- ] effects.<ref name="pmid14664351">{{cite journal | vauthors = Sinclair MD | title = A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice | journal = The Canadian Veterinary Journal | volume = 44 | issue = 11 | pages = 885–97 | date = November 2003 | pmid = 14664351 | pmc = 385445 }}</ref>
It is often used as the ] salt, medetomidine hydrochloride, a crystalline white solid that can be administered as an intravenous drug solution with sterile water.{{cn|date=August 2024}}

==Veterinary use==

In ], medetomidine is used as both a surgical and ] in combinations with opioids (], ] etc.) as premedication (before a ]) in healthy cats and dogs. It is sometimes used in combination with butorphanol and ] (given IM) to produce general anaesthesia for short periods in healthy, but fractious felines, that will not allow an intravenous induction agent to be given providing a good degree of muscle relaxation. It has also been used in combination with ] (or ]), ] and ketamine in constant rate infusion analgesia in canines. It is often used in so called ] for this analgesic effect. It is thought that this family of drugs has a degree of analgesic action, though this is, in comparison to the ] effect, minor.

It can be given by ] (IM), ] (SC) or ] (IV). When delivered intravenously, a significantly decreased dose is used. Some authors suggest a ] route is also effective. It is not recommended for diabetics, it is contraindicated in patients with cardiac disease.

Due to its potent sedative effects it is commonly used in more aggressive animals, where a drug combination with a lesser effect (such as ] plus an ], or an opioid plus a ]) would not allow the administration of the inductive agent without risk to the veterinarian. As such the use of alpha-two agonists is only recommended in healthy animals.

===Side effects===
Following administration, marked peripheral ] and ] are noted.<ref name=novartis>{{cite web | work = Novartis Animal Health Canada | title = Domitor | url = http://www.ah.ca.novartis.com/product/domitor.html | date = 2003 | archive-url = https://web.archive.org/web/20070924070246/http://www.ah.ca.novartis.com/product/domitor.html | archive-date = 2007-09-24 }}</ref> Often the dosage of induction agents (e.g. ]) may be drastically reduced, as may the volumes of anesthetic gases (i.e. ], ], ]) used to maintain general anesthesia.

Its effects can be reversed using ] distributed as Antisedan by Pfizer. IV use of atipamezole is not licensed, IM is the preferred route. ] may also be used in an emergency situation, but is not licensed.

==Use in marine paint==
The free base form of medetomidine is sold as '''Selektope''' as an ] substance in marine paints.<ref name =selektope>{{cite web |last1=Chaabane |first1=Philip | name-list-style = vanc |title=The Selektope Story |url=https://www.pcimag.com/ext/resources/WhitePapers/2016/The-Selektope-Story-v2.pdf |publisher=PCI Magazine |access-date=12 December 2018}}</ref> It is mainly effective against ], as shown in vitro with ].<ref name="Dahl">{{Cite journal |vauthors=Dahlström M, Mårtensson LG, Jonsson PR, Arnebrant T, Elwing H |date=November 2000 |title=Surface active adrenoceptor compounds prevent the settlement of cyprid larvae of Balanus improvisus. |journal=Biofouling |volume=16 |issue=2–4 |pages=191–203 |doi=10.1080/08927010009378444 |bibcode=2000Biofo..16..191D |s2cid=85603381}}</ref> It has also shown effect on other hard fouling like ]. When the barnacle cyprid larva encounters a surface containing medetomidine the molecule interacts with the ] in the larva. This causes the settling larva to increase its kicking to more than 100 kicks per minute, which makes becoming sessile nearly impossible.<ref name="Lind">{{Cite journal |display-authors=6 |vauthors=Lind U, Alm Rosenblad M, Hasselberg Frank L, Falkbring S, Brive L, Laurila JM, Pohjanoksa K, Vuorenpää A, Kukkonen JP, Gunnarsson L, Scheinin M, Mårtensson Lindblad LG, Blomberg A |date=August 2010 |title=Octopamine receptors from the barnacle balanus improvisus are activated by the alpha2-adrenoceptor agonist medetomidine |url=https://www.researchgate.net/publication/44617476 |journal=Molecular Pharmacology |volume=78 |issue=2 |pages=237–48 |doi=10.1124/mol.110.063594 |pmid=20488921 |s2cid=17792301}}</ref> When the larva swims away from the surface, the effect disappears (reversible effect). The larva regains its pre-exposure function and can settle somewhere else.

==Illicit use in humans==
===Component of street drugs===
Medetomidine has been found as a component in street drug mixtures in the US starting in 2022,<ref name="mmwr" /><ref name="de Andrade Horn" /> containing synthetic opioids in a similar manner as ]-], such mixtures have been nicknamed "tranq" (short for tranquilizer). The combination of α2 adrenergic agonists with opioids are believed to greatly increase the sedative effects of each drug, which some drug users may perceive as a better or more potent product. The Center for Forensic Science Research and Education (CFSRE) first identified a synthetic opioid blend containing fentanyl and medetomidine sold in Maryland in July, 2023. Additional detections in late 2023 found similar medetomidine mixtures in Missouri, Colorado, Pennsylvania, California, and Maryland found in both drug material and the blood of patients experiencing overdoses.<ref>{{Cite web |title=Medetomidine Rapidly Proliferating Across USA — Implicated In Recreational Opioid Drug Supply & Causing Overdose Outbreaks |url=https://www.cfsre.org/nps-discovery/public-alerts/medetomidine-rapidly-proliferating-across-usa-implicated-in-recreational-opioid-drug-supply-causing-overdose-outbreaks |access-date=2024-06-12 |website=www.cfsre.org}}</ref><ref>https://www.cfsre.org/images/monographs/Medetomidine-New-Drug-Monograph-NPS-Discovery-112723.pdf {{Bare URL PDF|date=August 2024}}</ref><ref>https://www.cfsre.org/images/content/reports/public_alerts/Public_Alert_Medetomidine_052024.pdf {{Bare URL PDF|date=August 2024}}</ref><ref>{{Cite web |last=Nelson |first=Sarah |title=What to know about medetomidine, the latest sedative found in illicit Indy drug supplies |url=https://www.indystar.com/story/news/crime/2024/05/24/what-to-know-about-medetomidine-the-latest-threat-in-street-drugs/73837879007/ |access-date=2024-06-12 |website=The Indianapolis Star |language=en-US}}</ref><ref name="de Andrade Horn" />

In January 2024 drug mixtures containing medetomidine were identified in the Canadian city of Toronto, ON. In April, 2024 and May, 2024 medetomidine was found in a mixture containing fentanyl and xylazine in Philadelphia, PA<ref>{{Cite web |last=Whelan |first=Aubrey |date=2024-05-18 |title=Philly health officials detect a veterinary sedative more powerful than xylazine in drug samples |url=https://www.inquirer.com/health/medetomidine-nitazenes-philadelphia-drug-overdoses-20240518.html |access-date=2024-06-12 |website= |language=en}}</ref> and Pittsburgh, PA. Cases of overdose in Chicago from medetomidine/fentanyl mixtures have been reported In May, 2024.<ref>{{Cite web |last=Dodge |first=John |date=2024-05-20 |title=Powerful animal sedative likely cause of overdose spike in Chicago - CBS Chicago |url=https://www.cbsnews.com/chicago/news/powerful-animal-sedative-likely-cause-of-overdose-spike-in-chicago/ |access-date=2024-06-12 |website=www.cbsnews.com |language=en-US}}</ref> Massachusetts reported its first cases in August 2024.<ref>{{Cite news| title = 'More toxic': Potent sedative triggering unexpected spike in overdoses, Mass. hospital warns| work = Boston 25 News| access-date = 2024-08-14| date = 2024-08-13| url = https://www.boston25news.com/news/local/more-toxic-potent-sedative-triggering-unexpected-spike-opioid-overdoses-mass-hospital-warns/Y7XMSFG6GVGFHBYCLXYZXFUVOI/}}</ref>

Medetomidine does not respond to ], complicating the medical response to overdoses. During summer 2024 there were "mass overdose events" linked to medetomidine adulterated drugs in Chicago and Philadelphia. Emergency room doctors in Philadelphia reported waves of overdose patients coming in with unusually low heart rates. Public health advisories were issued. Experts warned that it was not business as usual for first responders, emergency room personnel or drug users. One researcher compared experimenting with the current drug supply to "playing Russian roulette".<ref>{{cite news |title=Gangs mix another potent sedative into U.S. street drugs causing 'mass overdoses' |work=NPR |url=https://www.npr.org/2024/05/31/nx-s1-4974959/medetomidine-overdose-fentanyl-sedative}}</ref>

===Other criminal use===
Medetomidine was found in combination with the mu-opioid antagonist and kappa-opioid agonist ] and sedative dopamine antagonist tranquilizer ] in the blood of a 49-year old female homicide victim from Colorado that went missing after a bike ride in 2020. Such a mixture wouldn't be used for recreational use and would instead likely produce ] with heavy sedative effects that may render a person immobile or unable to defend themselves.<ref name="coloradosun">{{Cite web |last=Prentzel |first=Olivia |date=2024-04-29 |title=Suzanne Morphew's death was a homicide and she had tranquilizer in her system, autopsy reveals |url=http://coloradosun.com/2024/04/29/suzanne-morphew-autopsy-homicide/ |access-date=2024-06-12 |website=The Colorado Sun |language=en-US}}</ref><ref name="9news">{{Cite web |date=2024-04-29 |title=Suzanne Morphew autopsy: Here are the drugs that were found in her body |url=https://www.9news.com/article/news/crime/suzanne-morphew-autopsy-butorphanol-azaperone-medetomidine/73-4b914844-3af9-49a3-86df-01706b957fc4 |access-date=2024-06-12 |website=KUSA.com |language=en-US}}</ref><ref name="kdvr">{{Cite web |date=2024-04-29 |title=Suzanne Morphew's autopsy finds animal tranquilizer, other drugs in system |url=https://kdvr.com/news/local/suzanne-morphews-autopsy-finds-animal-tranquilizer-other-drugs-in-system/ |access-date=2024-06-12 |website=FOX31 Denver |language=en-US}}</ref>

== References ==
{{reflist}}

== Further reading ==
* {{cite book |title= Small Animal Surgery|last= Harari|first= Joseph | name-list-style = vanc |year= 1996|publisher= Williams and Wilkins|isbn= 978-0-683-03910-8}}

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