| Revision as of 00:11, 15 October 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{drugbox}} (changes to verified fields - updated '') per Chem/Drugbox validation (report errors or bugs)← Previous edit | Latest revision as of 01:23, 20 December 2024 edit undoCitation bot (talk | contribs)Bots5,431,788 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 | ||
| (113 intermediate revisions by 55 users not shown) | |||
| Line 1: | Line 1: | ||
| {{Short description|Chemical compound}} | |||
| {{more footnotes|date=January 2016}} | |||
| {{Drugbox | {{Drugbox | ||
| | Verifiedfields = changed | | Verifiedfields = changed | ||
| | Watchedfields = changed | |||
| | verifiedrevid = |
| verifiedrevid = 462101496 | ||
| | IUPAC_name = (''RS'')-4--3''H''-imidazole | | IUPAC_name = (''RS'')-4--3''H''-imidazole | ||
| | image = Medetomidine.svg | | image = Medetomidine.svg | ||
| | |
| chirality = ] | ||
| | drug_name = Medetomidine | |||
| <!--Clinical data--> | <!--Clinical data--> | ||
| | tradename = | | tradename = | ||
| Line 18: | Line 19: | ||
| | 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--> | ||
| Line 25: | Line 26: | ||
| | metabolism = | | metabolism = | ||
| | elimination_half-life = | | elimination_half-life = | ||
| | excretion = |
| excretion = | ||
| <!--Identifiers--> | <!--Identifiers--> | ||
| | CAS_number_Ref = {{cascite|changed|??}} | |||
| | CAS_number = 86347-14-0 | | CAS_number = 86347-14-0 | ||
| | ATCvet = yes | | ATCvet = yes | ||
| Line 34: | Line 36: | ||
| | ATC_supplemental = | | ATC_supplemental = | ||
| | PubChem = 68602 | | PubChem = 68602 | ||
| | DrugBank_Ref = {{drugbankcite| |
| 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| |
| 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| |
| ChEBI_Ref = {{ebicite|correct|EBI}} | ||
| | ChEBI = 48552 | | ChEBI = 48552 | ||
| | ChEMBL_Ref = {{ebicite|correct|EBI}} | | ChEMBL_Ref = {{ebicite|correct|EBI}} | ||
| Line 50: | Line 52: | ||
| | 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( |
||
| | 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) | ||
| Line 60: | Line 59: | ||
| }} | }} | ||
| '''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> | |||
| '''Medetomidine''' is a synthetic drug used as both a surgical ] and ] often used as the ] salt medetomidine hydrochloride. It is a crystalline white alpha-two ]<ref name="pmid14664351">{{cite journal |author=Sinclair MD |title=A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice |journal=Can. Vet. J. |volume=44 |issue=11 |pages=885–97 |year=2003 |month=November |pmid=14664351 |pmc=385445 |doi= |url=}}</ref> that can be administered as an intravenous drug solution with sterile water. It is currently 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'''. Other alpha-two agonists used in veterinary medicine include ] and ], but their use is less common in small animal surgery. The marketed product is a racemic mixture of 2 stereoisomers; ] is the compound with more useful effects, and is now marketed as Dexdomitor. | |||
| <!-- Side effects and mechanism --> | |||
| The free base form of medetomidine is distributed by the Swedish company I-Tech AB under the product name '''Selektope''' for use as an antifouling substance in marine paints. | |||
| 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 --> | |||
| ==Uses== | |||
| 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. | |||
| ===In veterinary medicine=== | |||
| ⚫ | |||
| ⚫ | Due to its potent sedative effects it is commonly used in more aggressive animals, where a drug |
||
| 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> | |||
| ⚫ | Following administration, marked peripheral ] and ] are noted. Often the dosage of induction agents ( |
||
| ==History== | |||
| 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. It provides a good degree of muscle relaxation, an important factor in Ketamine based anaethesia protocols. | |||
| Medetomidine was developed by ] and launched in 2007.<ref name=Orion/> | |||
| ==Pharmacology== | |||
| Medetomidine 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. | |||
| 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== | ||
| It is thought that this family of drugs has a degree of analgesic action, though this is, in comparison to the sedative effect, minor. | |||
| 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. | |||
| ⚫ | == |
||
| Medetomidine can be used as an ] substance in marine paint. It is mainly effective against ], but has also shown effect on other hard fouling like ]. When the barnacle cyprid larva encounters a surface containing medetomidine the molecule enters the octopamine receptor in the larva. This makes the larva legs start kicking and it cannot settle to the painted surface. When the larva swims away from the surface, the effect disappears (reversible effect).The larva regain its function and can settle somewhere else. | |||
| ⚫ | 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. | ||
| ==Reversal of effects== | |||
| ⚫ | Its effects can be reversed using ] |
||
| ⚫ | 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. | ||
| ==See also== | |||
| ⚫ | |||
| == |
===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. | ||
| {{refstyle}} | |||
| <references/> | |||
| * Novartis Animal Health Canada . 2003. <br />Harari, J. ''Small Animal Surgery''. Williams and Wilkins, Media, PA. 1996. | |||
| ⚫ | 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. | ||
| * Ulrika Lind, Magnus A Rosenblad, Linda Hasselberg Frank, Susanna Falkbring, Lars Brive, Jonne M Laurila, Katariina Pohjanoksa, Anne Vuorenpaa, Jyrki P Kukkonen, Lina Gunnarsson, Mika Scheinin, Lena G.E. Martensson Lindblad, and Anders Blomberg (Fast Forward 20 May 2010) Molecular Pharmacology Aug 1, 2010; 78 (2) | |||
| ⚫ | ==Use in marine paint== | ||
| * Dahlström M, Martensson LGE, Jonsson PR, Arnebrant T and Elwing H (2000) | |||
| 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}} | |||
| ⚫ | ] | ||
| ] | ] | ||
| ⚫ | ] | ||
| ⚫ | ] | ||
| ] | |||
| ] | |||
| ] | |||
| ] | ] | ||
| ] | |||
| ] | |||
Latest revision as of 01:23, 20 December 2024
Chemical compound | This article includes a list of general references, but it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (January 2016) (Learn how and when to remove this message) |
 | |
| Clinical data | |
|---|---|
| AHFS/Drugs.com | Monograph |
| ATCvet code | |
| Legal status | |
| Legal status |
|
| Identifiers | |
IUPAC name
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.242.450  |
| Chemical and physical data | |
| Formula | C13H16N2 |
| Molar mass | 200.285 g·mol |
| 3D model (JSmol) | |
| Chirality | Racemic mixture |
SMILES
| |
InChI
| |
| (what is this?) (verify) | |
Medetomidine is a veterinary anesthetic drug with potent sedative effects and emerging illicit drug adulterant.
It is a racemic mixture of two stereoisomers, levomedetomidine and dexmedetomidine, the latter being the isomer with the pharmacologic effect as an alpha 2- adrenergic agonist. Effects can be reversed using atipamezole.
It was developed by Orion Pharma. It is approved for dogs in the United States, and distributed in the United States by Pfizer Animal Health and by Novartis 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.
History
Medetomidine was developed by Orion Pharma and launched in 2007.
Pharmacology
Medetomidine is a racemic mixture of two optical or stereoisomers, levomedetomidine and dexmedetomidine. The latter causes the alpha 2- adrenergic agonist effects. It is often used as the hydrochloride salt, medetomidine hydrochloride, a crystalline white solid that can be administered as an intravenous drug solution with sterile water.
Veterinary use
In veterinary anesthesia, medetomidine is used as both a surgical and analgesic in combinations with opioids (butorphanol, buprenorphine etc.) as premedication (before a general anesthetic) in healthy cats and dogs. It is sometimes used in combination with butorphanol and ketamine (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 morphine (or methadone), lidocaine and ketamine in constant rate infusion analgesia in canines. It is often used in so called microdoses 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 sedative effect, minor.
It can be given by intramuscular injection (IM), subcutaneous injection (SC) or intravenous injection (IV). When delivered intravenously, a significantly decreased dose is used. Some authors suggest a sublingual 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 acepromazine plus an opioid, or an opioid plus a benzodiazepine) 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 vasoconstriction and bradycardia are noted. Often the dosage of induction agents (e.g. propofol) may be drastically reduced, as may the volumes of anesthetic gases (i.e. halothane, isoflurane, sevoflurane) used to maintain general anesthesia.
Its effects can be reversed using atipamezole distributed as Antisedan by Pfizer. IV use of atipamezole is not licensed, IM is the preferred route. Yohimbine 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 antifouling substance in marine paints. It is mainly effective against barnacles, as shown in vitro with Balanus improvisus. It has also shown effect on other hard fouling like tube worms. When the barnacle cyprid larva encounters a surface containing medetomidine the molecule interacts with the octopamine receptor 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. 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, containing synthetic opioids in a similar manner as xylazine-fentanyl, 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.
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 and Pittsburgh, PA. Cases of overdose in Chicago from medetomidine/fentanyl mixtures have been reported In May, 2024. Massachusetts reported its first cases in August 2024.
Medetomidine does not respond to naloxone, 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".
Other criminal use
Medetomidine was found in combination with the mu-opioid antagonist and kappa-opioid agonist Butorphanol and sedative dopamine antagonist tranquilizer Azaperone 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 dysphoria with heavy sedative effects that may render a person immobile or unable to defend themselves.
References
- ^ de Andrade Horn P, Berida TI, Parr LC, Bouchard JL, Jayakodiarachchi N, Schultz DC, Lindsley CW, Crowley ML (October 2024). "Classics in Chemical Neuroscience: Medetomidine". ACS Chem Neurosci. 15 (21): 3874–3883. doi:10.1021/acschemneuro.4c00583. PMC 11587509. PMID 39405508.
- ^ "Achievements". Orion Corporation. Archived from the original on March 15, 2013.
- ^ Chaabane P. "The Selektope Story" (PDF). PCI Magazine. Retrieved 12 December 2018.
- ^ Schwarz, Evan S. (2024). "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". MMWR. Morbidity and Mortality Weekly Report. 73 (30): 672–674. doi:10.15585/mmwr.mm7330a3. ISSN 0149-2195. PMC 11305408. PMID 39088371.
- Sinclair MD (November 2003). "A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice". The Canadian Veterinary Journal. 44 (11): 885–97. PMC 385445. PMID 14664351.
- "Domitor". Novartis Animal Health Canada. 2003. Archived from the original on 2007-09-24.
- Dahlström M, Mårtensson LG, Jonsson PR, Arnebrant T, Elwing H (November 2000). "Surface active adrenoceptor compounds prevent the settlement of cyprid larvae of Balanus improvisus". Biofouling. 16 (2–4): 191–203. Bibcode:2000Biofo..16..191D. doi:10.1080/08927010009378444. S2CID 85603381.
- Lind U, Alm Rosenblad M, Hasselberg Frank L, Falkbring S, Brive L, Laurila JM, et al. (August 2010). "Octopamine receptors from the barnacle balanus improvisus are activated by the alpha2-adrenoceptor agonist medetomidine". Molecular Pharmacology. 78 (2): 237–48. doi:10.1124/mol.110.063594. PMID 20488921. S2CID 17792301.
- "Medetomidine Rapidly Proliferating Across USA — Implicated In Recreational Opioid Drug Supply & Causing Overdose Outbreaks". www.cfsre.org. Retrieved 2024-06-12.
- https://www.cfsre.org/images/monographs/Medetomidine-New-Drug-Monograph-NPS-Discovery-112723.pdf
- https://www.cfsre.org/images/content/reports/public_alerts/Public_Alert_Medetomidine_052024.pdf
- Nelson, Sarah. "What to know about medetomidine, the latest sedative found in illicit Indy drug supplies". The Indianapolis Star. Retrieved 2024-06-12.
- Whelan, Aubrey (2024-05-18). "Philly health officials detect a veterinary sedative more powerful than xylazine in drug samples". Retrieved 2024-06-12.
- Dodge, John (2024-05-20). "Powerful animal sedative likely cause of overdose spike in Chicago - CBS Chicago". www.cbsnews.com. Retrieved 2024-06-12.
- "'More toxic': Potent sedative triggering unexpected spike in overdoses, Mass. hospital warns". Boston 25 News. 2024-08-13. Retrieved 2024-08-14.
- "Gangs mix another potent sedative into U.S. street drugs causing 'mass overdoses'". NPR.
- Prentzel, Olivia (2024-04-29). "Suzanne Morphew's death was a homicide and she had tranquilizer in her system, autopsy reveals". The Colorado Sun. Retrieved 2024-06-12.
- "Suzanne Morphew autopsy: Here are the drugs that were found in her body". KUSA.com. 2024-04-29. Retrieved 2024-06-12.
- "Suzanne Morphew's autopsy finds animal tranquilizer, other drugs in system". FOX31 Denver. 2024-04-29. Retrieved 2024-06-12.
Further reading
- Harari J (1996). Small Animal Surgery. Williams and Wilkins. ISBN 978-0-683-03910-8.