Levamisole

{{Short description|Chemical compound}} {{Use dmy dates|date=March 2024}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | image = Levamisole.svg | image_class = skin-invert-image | width = 180 | alt = Skeletal formula of levamisole | image2 = Levamisole molecule ball.png | image_class2 = bg-transparent | alt2 = Ball-and-stick model of the levamisole molecule

| pronounce = | tradename = Ergamisol, others | Drugs.com = {{drugs.com|CONS|levamisole}} | MedlinePlus = a697011 | DailyMedID = Levamisole | pregnancy_AU =  | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = By mouth | class = | ATC_prefix = P02 | ATC_suffix = CE01 | ATC_supplemental = {{ATCvet|P52|AE01}}

| IUPAC_name = (''S'')-6-Phenyl-2,3,5,6-tetrahydroimidazo[2,1-''b''] [1,3]thiazole | C=11 | H=12 | N=2 | S=1 | SMILES = N\2=C1/SCCN1C[C@@H]/2c3ccccc3 | StdInChI = 1S/C11H12N2S/c1-2-4-9(5-3-1)10-8-13-6-7-14-11(13)12-10/h1-5,10H,6-8H2/t10-/m1/s1 | StdInChI_comment = | StdInChIKey = HLFSDGLLUJUHTE-SNVBAGLBSA-N | density = 1.31 | density_notes = | melting_point = 60 | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = 210 | sol_units = hydrochloride | specific_rotation = }}

'''Levamisole''', sold under the brand name '''Ergamisol''' among others, is a medication used to treat parasitic worm infections, specifically ascariasis and hookworm infections.<ref>{{cite journal | vauthors = Keiser J, Utzinger J | title = Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis | journal = JAMA | volume = 299 | issue = 16 | pages = 1937–48 | date = April 2008 | pmid = 18430913 | doi = 10.1001/jama.299.16.1937 }}</ref> It is taken by mouth.<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 978-92-4-154765-9 | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | publisher = World Health Organization | hdl-access=free | pages=86, 590}}</ref>

Side effects may include abdominal pain, vomiting, headache, and dizziness.<ref name=WHO2008/> Use is not recommended during breastfeeding or the third trimester of pregnancy.<ref name=WHO2008/> Serious side effects may include an increased risk of infection.<ref name=Cons2016>{{cite web|title=Levamisole Advanced Patient Information - Drugs.com|url=https://www.drugs.com/cons/levamisole.html|website=www.drugs.com|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220222556/https://www.drugs.com/cons/levamisole.html|archive-date=20 December 2016}}</ref> It belongs to the anthelmintic class of medications.<ref name=Cons2016/>

Levamisole was invented in 1966 in Belgium by Janssen Pharmaceuticals.<ref>{{cite book| vauthors = Prevenier W, Howelland M |title=From reliable sources: an introduction to historical methods|date=2001|publisher=Cornell university press|location=Ithaca|isbn=978-0-8014-8560-2|page=77|edition=1st |url=https://books.google.com/books?id=wSqgwOZPjJ4C&pg=PA77|url-status=live|archive-url=https://web.archive.org/web/20170910151722/https://books.google.com/books?id=wSqgwOZPjJ4C&pg=PA77|archive-date=10 September 2017}}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">{{cite book | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Levamisole is also used as a dewormer for cattle.<ref name="Valcor FDA label" /><ref>{{cite book| vauthors = Taylor MA, Coop RL, Wall RL |title=Veterinary Parasitology|date=2015|publisher=John Wiley & Sons|isbn=978-1-119-07367-3|page=329|url=https://books.google.com/books?id=ta7YCgAAQBAJ&pg=PA329|language=en|url-status=live|archive-url=https://web.archive.org/web/20170910151722/https://books.google.com/books?id=ta7YCgAAQBAJ&pg=PA329|archive-date=10 September 2017}}</ref> It is also often used as a cutting agent in illegal cocaine.

In February 2026, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency recommended that medicines containing levamisole be withdrawn from the EU market.<ref name="EMA 20260213" /> This follows an EU-wide review which concluded that the benefits of these medicines no longer outweigh their risks for the treatment of parasitic worm infections in adults and children.<ref name="EMA 20260213">{{cite press release | title=EMA recommends withdrawal of marketing authorisations for levamisole medicines | website=European Medicines Agency (EMA) | date=13 February 2026 | url=https://www.ema.europa.eu/en/news/ema-recommends-withdrawal-marketing-authorisations-levamisole-medicines | access-date=15 February 2026}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>

==Medical uses==

===Worms=== Levamisole was originally used as an anthelmintic to treat worm infestations in both humans and animals. Levamisole works as a nicotinic acetylcholine receptor agonist that causes continued stimulation of the parasitic worm muscles, leading to paralysis.<ref>{{cite web|title=Levamisole | work = Martindale: The Complete Drug Reference |url=http://online.lexi.com/lco/action/doc/retrieve/docid/martindale_f/1351191| publisher =Lexicomp|access-date=21 April 2014|url-status=live|archive-url= https://web.archive.org/web/20161221163156/http://online.lexi.com/lco/action/doc/retrieve/docid/martindale_f/1351191|archive-date=21 December 2016}}</ref> Levamisole has gained prominence among aquarists as an effective treatment for ''Camallanus'' roundworm infestations in freshwater tropical fish.<ref>{{cite web | vauthors = Sanford S |title = Levamisole Hydrochloride: Its application and usage in freshwater aquariums |publisher = Loaches Online |year = 2007 |url = http://www.loaches.com/disease-treatment/levamisole-hydrochloride-1 |access-date = 27 February 2009 |url-status = live |archive-url = https://web.archive.org/web/20090301001606/http://www.loaches.com/disease-treatment/levamisole-hydrochloride-1 |archive-date = 1 March 2009 }}</ref> Levamisole has been used to treat small ruminant animals since the late 1960s.<ref>{{cite journal | vauthors = Harder A | title = Chemotherapeutic approaches to nematodes: current knowledge and outlook | journal = Parasitology Research | volume = 88 | issue = 3 | pages = 272–277 | date = March 2002 | pmid = 11954915 | doi = 10.1007/s00436-001-0535-x }}</ref> Levamisole-resistant parasitic worms are common in sheep farms in New Zealand,<ref>{{cite journal | vauthors = Waghorn TS, Leathwick DM, Rhodes AP, Lawrence KE, Jackson R, Pomroy WE, West DM, Moffat JR | title = Prevalence of anthelmintic resistance on sheep farms in New Zealand | journal = New Zealand Veterinary Journal | volume = 54 | issue = 6 | pages = 271–277 | date = December 2006 | pmid = 17151724 | doi = 10.1080/00480169.2006.36710 }}</ref> Uruguay,<ref>{{cite journal | vauthors = Nari A, Salles J, Gil A, Waller PJ, Hansen JW | title = The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: Uruguay | journal = Veterinary Parasitology | volume = 62 | issue = 3–4 | pages = 213–222 | date = April 1996 | pmid = 8686167 | doi = 10.1016/0304-4017(95)00908-6 }}</ref> Paraguay,<ref>{{cite journal | vauthors = Maciel S, Giménez AM, Gaona C, Waller PJ, Hansen JW | title = The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: Paraguay | journal = Veterinary Parasitology | volume = 62 | issue = 3–4 | pages = 207–212 | date = April 1996 | pmid = 8686166 | doi = 10.1016/0304-4017(95)00907-8 }}</ref> and Brazil.<ref>{{cite journal | vauthors = Echevarria F, Borba MF, Pinheiro AC, Waller PJ, Hansen JW | title = The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: Brazil | journal = Veterinary Parasitology | volume = 62 | issue = 3–4 | pages = 199–206 | date = April 1996 | pmid = 8686165 | doi = 10.1016/0304-4017(95)00906-x }}</ref>

===Other=== Levamisole has been used to treat a variety of dermatologic conditions, including skin infections, leprosy, warts, lichen planus, and aphthous ulcers.<ref>{{cite journal | vauthors = Scheinfeld N, Rosenberg JD, Weinberg JM | title = Levamisole in dermatology: a review | journal = American Journal of Clinical Dermatology | volume = 5 | issue = 2 | pages = 97–104 | year = 2004 | pmid = 15109274 | doi = 10.2165/00128071-200405020-00004 | s2cid = 1171779 }}</ref>

An interesting side effect these reviewers reported in passing was "neurologic excitement". Later papers, from the Janssen group and others, indicate levamisole and its enantiomer, dexamisole, have some mood-elevating or antidepressant properties, although this was never a marketed use of the drug.<ref>{{cite journal | vauthors = Vanhoutte PM, Van Nueten JM, Verbeuren TJ, Laduron PM | title = Differential effects of the isomers of tetramisole on adrenergic neurotransmission in cutaneous veins of dog | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 200 | issue = 1 | pages = 127–40 | date = January 1977 | doi = 10.1016/S0022-3565(25)30750-0 | pmid = 189006 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=189006 | url-access = subscription }}</ref><ref>{{cite journal | vauthors = Przegaliński E, Bigajska K, Siwanowicz J | title = Psychopharmacological profile of dexamisole | journal = Polish Journal of Pharmacology and Pharmacy | volume = 32 | issue = 1 | pages = 21–9 | year = 1980 | pmid = 7454609 }}</ref>

== Adverse effects == One of the more serious side effects of levamisole is agranulocytosis, or the depletion of the white blood cells. In particular, neutrophils appear to be affected the most. This occurs in 0.08–5% of the studied populations.<ref>{{cite web |title=Levamisole |url=http://www.deadiversion.usdoj.gov/drug_chem_info/levamisole.pdf |publisher=DEA |access-date=21 April 2014 |url-status=live |archive-url=https://web.archive.org/web/20131017084451/http://www.deadiversion.usdoj.gov/drug_chem_info/levamisole.pdf |archive-date=17 October 2013}}</ref>

It has been used as an adulterant in cocaine, resulting in serious side effects that present as levamisole induced necrosis syndrome, in which erythematous painful papules can appear almost anywhere on skin.<ref name="mmwr">{{cite journal | title = Agranulocytosis associated with cocaine use - four States, March 2008-November 2009 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 58 | issue = 49 | pages = 1381–5 | date = December 2009 | pmid = 20019655 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5849a3.htm | author1 = Centers for Disease Control Prevention (CDC) }}</ref><ref>{{cite journal | vauthors = Chang A, Osterloh J, Thomas J | title = Levamisole: a dangerous new cocaine adulterant | journal = Clinical Pharmacology and Therapeutics | volume = 88 | issue = 3 | pages = 408–11 | date = September 2010 | pmid = 20668440 | doi = 10.1038/clpt.2010.156 | s2cid = 31414939 }}</ref><ref>{{cite web |title=Cocaine powder: review of its prevalence, patterns of use and harm |url=https://www.gov.uk/government/publications/cocaine-powder-review-of-its-prevalence-patterns-of-use-and-harm |date=12 March 2015 |publisher=Advisory Council on the Misuse of Drugs }}</ref>

In September 2025, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency started a review of medicines containing levamisole, authorized in four countries of the European Union to treat infections caused by parasitic worms in adults and children.<ref name="EMA 20250905" /> The review follows concerns about a risk of leukoencephalopathy with levamisole, a potentially serious condition that damages the white matter of the brain.<ref name="EMA 20250905" /> White matter is made of nerve fibres covered by a protective layer called myelin, which allows efficient communication between different parts of the brain.<ref name="EMA 20250905" /> Leukoencephalopathy can be life-threatening and debilitating, especially when left undiagnosed or untreated.<ref name="EMA 20250905" /> It may lead to a range of neurological symptoms, including but not limited to, confusion, weakness or impaired muscle function, difficulties with movement coordination, and impaired or lost speech or vision.<ref name="EMA 20250905" /> Leukoencephalopathy has already been identified as a potential risk with levamisole, and the product information of levamisole medicines include the general term encephalopathy (a group of brain dysfunction conditions).<ref name="EMA 20250905">{{cite web | title=PRAC starts safety review of levamisole, a medicine used to treat parasitic worm infections | website=European Medicines Agency (EMA) | date=5 September 2025 | url=https://www.ema.europa.eu/en/news/prac-starts-safety-review-levamisole-medicine-used-treat-parasitic-worm-infections | access-date=28 September 2025}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>

In February 2026, the PRAC recommended that medicines containing levamisole be withdrawn from the EU market.<ref name="EMA 20260213" /> This follows an EU-wide review which concluded that the benefits of these medicines no longer outweigh their risks for the treatment of parasitic worm infections in adults and children.<ref name="EMA 20260213" />

== Metabolism == Levamisole is readily absorbed from the gastrointestinal tract and metabolized in the liver. Its time to peak plasma concentration is 1.5–2 hours. The plasma elimination half-life is fairly quick at 3–4 hours which can contribute to not detecting levamisole intoxication. The metabolite half-life is 16 hours. Levamisole's excretion is primarily through the kidneys, with about 70% being excreted over 3 days. Only about 5% is excreted as unchanged levamisole.<ref>{{cite journal | vauthors = Kouassi E, Caillé G, Léry L, Larivière L, Vézina M | title = Novel assay and pharmacokinetics of levamisole and p-hydroxylevamisole in human plasma and urine | journal = Biopharmaceutics & Drug Disposition | volume = 7 | issue = 1 | pages = 71–89 | year = 1986 | pmid = 3754161 | doi = 10.1002/bdd.2510070110 }}</ref><ref>{{cite journal | vauthors = Luyckx M, Rousseau F, Cazin M, Brunet C, Cazin JC, Haguenoer JM, Devulder B, Lesieur I, Lesieur D, Gosselin P, Adenis L, Cappelaere P, Demaille A | title = Pharmacokinetics of levamisole in healthy subjects and cancer patients | journal = European Journal of Drug Metabolism and Pharmacokinetics | volume = 7 | issue = 4 | pages = 247–54 | year = 1982 | pmid = 7166176 | doi = 10.1007/bf03189626 | s2cid = 13206196 }}</ref>

Drug testing of racehorse urine has led to the revelation that among levamisole equine metabolites are both pemoline and aminorex, stimulants that are forbidden by racing authorities.<ref>{{cite journal | vauthors = Gutierrez J, Eisenberg RL, Koval NJ, Armstrong ER, Tharappel J, Hughes CG, Tobin T | title = Pemoline and tetramisole 'positives' in english racehorses following levamisole administration | journal = Irish Veterinary Journal | volume = 63 | issue = 8 | article-number = 498 | date = August 2010 | pmid = 21777496 | pmc = 4177197 | doi = 10.1186/2046-0481-63-8-498 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ho EN, Leung DK, Leung GN, Wan TS, Wong AS, Wong CH, Soma LR, Rudy JA, Uboh C, Sams R | title = Aminorex and rexamino as metabolites of levamisole in the horse | journal = Analytica Chimica Acta | volume = 638 | issue = 1 | pages = 58–68 | date = April 2009 | pmid = 19298880 | doi = 10.1016/j.aca.2009.02.033 | bibcode = 2009AcAC..638...58H }}</ref><ref>{{cite book | vauthors = Scarth, etal | chapter = The use of ''in vitro'' drug metabolism studies to complement, reduce and refine ''in vivo'' administrations in medication and doping control. | veditors = Beresford GD, Howitt RG |title=Proceedings of the 18th International Conference of Racing analysts and Veterinarians (ICRAV), Queenstown, New Zealand |date=2012 |publisher=Dumnor Publishing, Limited |location=Auckland |isbn=978-0-473-22084-6 | pages = 213–222 }}</ref> Further testing confirmed aminorex in human and canine urine, meaning that both humans and dogs also metabolize levamisole into aminorex,<ref name="pmid21531521">{{cite journal | vauthors = Bertol E, Mari F, Milia MG, Politi L, Furlanetto S, Karch SB | title = Determination of aminorex in human urine samples by GC-MS after use of levamisole | journal = Journal of Pharmaceutical and Biomedical Analysis | volume = 55 | issue = 5 | pages = 1186–1189 | date = July 2011 | pmid = 21531521 | doi = 10.1016/j.jpba.2011.03.039 }}</ref> though it is unclear whether plasma aminorex is present at any appreciable level. Blood samples following oral administration of levamisole out to 172 hr post-dose did not demonstrate any plasma aminorex levels above that of the limit of quantification (LoQ). Additionally, in cocaine-positive plasma samples, of which 42% contained levamisole, aminorex was never reported at concentrations higher than LoQ.<ref>{{cite journal | vauthors = Hess C, Ritke N, Broecker S, Madea B, Musshoff F | title = Metabolism of levamisole and kinetics of levamisole and aminorex in urine by means of LC-QTOF-HRMS and LC-QqQ-MS | journal = Analytical and Bioanalytical Chemistry | volume = 405 | issue = 12 | pages = 4077–4088 | date = May 2013 | pmid = 23436169 | doi = 10.1007/s00216-013-6829-x | s2cid = 2222462 }}</ref>

==Detection in body fluids== Levamisole may be quantified in blood, plasma, or urine as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths involving adulterated street drugs. About 3% of an oral dose is eliminated unchanged in the 24-hour urine of humans. A post mortem blood levamisole concentration of 2.2 mg/L was present in a woman who died of a cocaine overdose.<ref>{{cite journal | vauthors = Vandamme TF, Demoustier M, Rollmann B | title = Quantitation of levamisole in plasma using high performance liquid chromatography | journal = European Journal of Drug Metabolism and Pharmacokinetics | volume = 20 | issue = 2 | pages = 145–9 | year = 1995 | pmid = 8582440 | doi = 10.1007/bf03226369 | s2cid = 9258640 }}</ref><ref>{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 9th | publisher = Biomedical Publications | location = Seal Beach, CA | date = 2011 | pages = 901–902 | url= http://www.biomedicalpublications.com/levamisole.pdf |access-date=22 January 2011 |archive-url= https://web.archive.org/web/20110910160556/http://www.biomedicalpublications.com/levamisole.pdf |archive-date=10 September 2011 }}</ref>

== Adulterant in illegal drugs == In the body, levamisole is converted into aminorex, a substance with amphetamine-like stimulant effects and a long duration of action.<ref>{{cite journal | vauthors = Solomon N, Hayes J | title = Levamisole: A High Performance Cutting Agent | journal = Academic Forensic Pathology | volume = 7 | issue = 3 | pages = 469–476 | date = September 2017 | doi = 10.23907/2017.039 | pmid = 31239995 | pmc = 6474566 }}</ref>

Beginning in early 2003, South American cartels started adding levamisole to bulk cocaine before shipping it to the United States (Valentino and Fuentecilla 2005).<ref>{{cite journal | vauthors = Buchanan JA, Oyer RJ, Patel NR, Jacquet GA, Bornikova L, Thienelt C, Shriver DA, Shockley LW, Wilson ML, Hurlbut KM, Lavonas EJ | title = A confirmed case of agranulocytosis after use of cocaine contaminated with levamisole | journal = Journal of Medical Toxicology | volume = 6 | issue = 2 | pages = 160–164 | date = June 2010 | pmid = 20358411 | doi = 10.1007/s13181-010-0060-3 | pmc = 3550277 }}</ref>

Levamisole has increasingly been used as a cutting agent in cocaine sold around the globe with the highest incidence being in the United States. In 2008–2009, levamisole was found in 69% of cocaine samples seized by the Drug Enforcement Administration (DEA).<ref name="mmwr"/> By April 2011, the DEA reported the adulterant was found in 82% of seizures.<ref name="abc20110623">{{cite news | vauthors = Moisse K | title = Cocaine Laced With Veterinary Drug Levamisole Eats Away at Flesh | date = 23 June 2011 | url = https://abcnews.go.com/Health/Wellness/flesh-eating-cocaine-laced-veterinary-drug-levamisole/story?id=13902353 | work = ABC News | access-date = 23 June 2011 | url-status = live | archive-url = https://web.archive.org/web/20110625225534/https://abcnews.go.com/Health/Wellness/flesh-eating-cocaine-laced-veterinary-drug-levamisole/story?id=13902353 | archive-date = 25 June 2011 }}</ref> By October 2017, this figure had risen further, with the DEA reporting that 87% of seized and analyzed cocaine bricks in the United States contained levamisole, making it the most common adulterant in cocaine at that time.<ref>{{Cite web|url=https://www.dea.gov/sites/default/files/2018-07/DIR-040-17_2017-NDTA.pdf|title=2017 National drug threat assessment |website=www.dea.gov}}</ref>

Levamisole adds bulk and weight to powdered cocaine (whereas other adulterants produce smaller "rocks" of cocaine) and makes the drug appear purer.<ref>{{cite news|url=https://news.yahoo.com/s/hsn/contaminatedcocainecancausefleshtorot;_ylt=Arpc.e2vZk4K0VyhIadneKes0NUE;_ylu=X3oDMTRhMzAybmR2BGFzc2V0A2hzbi8yMDEwMDYwMS9jb250YW1pbmF0ZWRjb2NhaW5lY2FuY2F1c2VmbGVzaHRvcm90BGNjb2RlA21vc3Rwb3B1bGFyBGNwb3MDOARwb3MDNQRwdANob21lX2Nva2UEc2VjA3luX2hlYWRsaW5lX2xpc3QEc2xrA2NvbnRhbWluYXRlZA--|title=Contaminated Cocaine Can Cause Flesh to Rot| vauthors = Doheny K |date=1 June 2010|work=Yahoo!|access-date=8 June 2010|archive-url=https://web.archive.org/web/20100607071126/http://news.yahoo.com/s/hsn/contaminatedcocainecancausefleshtorot|archive-date=7 June 2010}}</ref> In a series of investigative articles for ''The Stranger'', Brendan Kiley details other rationales for levamisole's rise as an adulterant: possible stimulant effects, a similar appearance to cocaine, and an ability to pass street purity tests.<ref name=kiley>{{cite news |title=The Mystery of the Tainted Cocaine | vauthors = Kiley B |url=http://www.thestranger.com/seattle/the-mystery-of-the-tainted-cocaine/Content?oid=4683741 |work=The Stranger |date=17 August 2010 |access-date=21 December 2010 |url-status=live |archive-url=https://web.archive.org/web/20101211143437/http://www.thestranger.com/seattle/the-mystery-of-the-tainted-cocaine/Content?oid=4683741 |archive-date=11 December 2010 }}</ref>

Levamisole suppresses the production of white blood cells, resulting in neutropenia and agranulocytosis. With the increasing use of levamisole as an adulterant, a number of these complications have been reported among cocaine users.<ref name="mmwr"/><ref name="annals">{{cite journal | vauthors = Zhu NY, Legatt DF, Turner AR | title = Agranulocytosis after consumption of cocaine adulterated with levamisole | journal = Annals of Internal Medicine | volume = 150 | issue = 4 | pages = 287–289 | date = February 2009 | pmid = 19153405 | doi = 10.7326/0003-4819-150-4-200902170-00102 }}</ref><ref>{{cite journal | vauthors = Kinzie E | title = Levamisole found in patients using cocaine | journal = Annals of Emergency Medicine | volume = 53 | issue = 4 | pages = 546–547 | date = April 2009 | pmid = 19303517 | doi = 10.1016/j.annemergmed.2008.10.017 | doi-access = free }}</ref> Levamisole has also been linked to a risk of vasculitis,<ref>{{cite journal | vauthors = Menni S, Pistritto G, Gianotti R, Ghio L, Edefonti A | title = Ear lobe bilateral necrosis by levamisole-induced occlusive vasculitis in a pediatric patient | journal = Pediatric Dermatology | volume = 14 | issue = 6 | pages = 477–479 | year = 1997 | pmid = 9436850 | doi = 10.1111/j.1525-1470.1997.tb00695.x | s2cid = 26527277 }}</ref> and two cases of vasculitic skin necrosis have been reported in users of cocaine adulterated with levamisole.<ref>{{cite journal | vauthors = Bradford M, Rosenberg B, Moreno J, Dumyati G | title = Bilateral necrosis of earlobes and cheeks: another complication of cocaine contaminated with levamisole | journal = Annals of Internal Medicine | volume = 152 | issue = 11 | pages = 758–759 | date = June 2010 | pmid = 20513844 | doi = 10.7326/0003-4819-152-11-201006010-00026 | doi-access = free }}</ref>

==Chemistry== The original synthesis at Janssen Pharmaceutica resulted in the preparation of a racemic mixture of two enantiomers, whose hydrochloride salt was reported to have a melting point of 264–265 °C; the free base of the racemate has a melting point of 87–89 °C. The racemic mixture is referred to as "tetramisole" - levamisole refers only to the levorotatory enantiomer of tetramisole.{{cn|date=December 2022}}

==Toxicity== The LD<sub>50</sub> (intravenous, mouse) is 22 mg/kg.<ref name = Sym>{{cite book | vauthors = Symoens J, DeCree J, Bever WV, Janssen PA | chapter = Levamisole | date = 1979 | title = Pharmacological and Biochemical Properties of Drug Substances | volume = 2 | veditors = Goldberg ME | pages = 407–464 | location = Washington | publisher = American Pharmaceutical Association | oclc = 1106595378 }}</ref>

== Laboratory use == Levamisole reversibly and uncompetitively inhibits most isoforms of alkaline phosphatase (e.g., human liver, bone, kidney, and spleen) except the intestinal and placental isoform.<ref name="pmid6169">{{cite journal | vauthors = Van Belle H | title = Alkaline phosphatase. I. Kinetics and inhibition by levamisole of purified isoenzymes from humans | journal = Clinical Chemistry | volume = 22 | issue = 7 | pages = 972–6 | date = July 1976 | doi = 10.1093/clinchem/22.7.972 | pmid = 6169| doi-access = free }}</ref><ref>{{cite journal|title=Levamisole inhibition of alkaline phosphatase and 5'-nucleotidase of bovine milk fat globule membranes|journal=International Journal of Biochemistry|vauthors=Khodaparast-Sharifi SH, Snow LD|year=1989|volume=21|issue=4|pages=401–405|doi=10.1016/0020-711X(89)90364-9|pmid=2545478}}</ref> It is thus used as an inhibitor along with substrate to reduce background alkaline phosphatase activity in biomedical assays involving detection signal amplification by intestinal alkaline phosphatase, for example in ''in situ'' hybridization or Western blot protocols.{{cn|date=December 2022}}

It is used to immobilize the nematode ''C. elegans'' on glass slides for imaging and dissection.<ref>{{cite web |url=http://genetics.wustl.edu/tslab/protocols/dissection-staining-in-situ/gonad-dissections/ |title=Gonad Dissections | Schedl Lab |access-date=15 May 2014 |url-status=live |archive-url=https://web.archive.org/web/20140517154147/http://genetics.wustl.edu/tslab/protocols/dissection-staining-in-situ/gonad-dissections/ |archive-date=17 May 2014 }} Schedl Lab Protocol for gonad dissections</ref>

In a ''C. elegans'' behavioral assay, analyzing the time course of paralysis provides information about the neuromuscular junction. Levamisole acts as an acetylcholine receptor agonist, which leads to muscle contraction. Continuing activation leads to paralysis. The time course of paralysis provides information about the acetylcholine receptors on the muscle. For example, mutants with fewer acetylcholine receptors may paralyze slower than wild type.<ref>{{cite journal | vauthors = Rand JB | title = Acetylcholine | journal = WormBook | pages = 1–21 | date = January 2007 | pmid = 18050502 | pmc = 4781110 | doi = 10.1895/wormbook.1.131.1 | url = https://www.ncbi.nlm.nih.gov/books/NBK19736/ }}</ref>

==Research== It has been studied as a method to stimulate the immune system as part of the treatment of cancer.<ref>{{cite journal | vauthors = Dillman RO | title = Cancer immunotherapy | journal = Cancer Biotherapy & Radiopharmaceuticals | volume = 26 | issue = 1 | pages = 1–64 | date = February 2011 | pmid = 21355777 | doi = 10.1089/cbr.2010.0902 }}</ref> It has also shown some efficacy in the treatment of nephrotic syndrome in children.<ref>{{cite journal | vauthors = Couderc A, Bérard E, Guigonis V, Vrillon I, Hogan J, Audard V, Baudouin V, Dossier C, Boyer O | title = [Treatments of steroid-dependent nephrotic syndrome in children] | journal = Archives de Pédiatrie | volume = 24 | issue = 12 | pages = 1312–1320 | date = December 2017 | pmid = 29146214 | doi = 10.1016/j.arcped.2017.09.002 }}</ref>

After being pulled from the market in the US and Canada in 1999 and 2003, respectively, levamisole has been tested in combination with fluorouracil to treat colon cancer. Evidence from clinical trials support its addition to fluorouracil therapy to benefit patients with colon cancer. In some of the leukemic cell line studies, both levamisole and tetramisole showed similar effect.<ref>(Chirigos et al. (1969, 1973, 1975)).</ref>

== Veterinary uses == The combination doramectin/levamisole, sold under the brand name Valcor, is indicated for the treatment and control of gastrointestinal roundworms, lungworms, grubs, sucking lice, and mange mites in cattle.<ref name="Valcor FDA label">{{cite web | title=Valcor- doramectin and levamisole injection, solution | website=DailyMed | date=13 August 2025 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ceeeee6b-011a-4d2f-a90a-d2958a9f12f9 | access-date=28 September 2025}}</ref> It is given by subcutaneous injection.<ref name="Valcor FDA label" />

== References == {{Reflist}}

Category:Anthelmintics Category:Janssen Pharmaceutica Category:Belgian inventions Category:Nicotinic agonists Category:Phosphatase inhibitors Category:World Health Organization essential medicines Category:Wikipedia medicine articles ready to translate Category:Withdrawn drugs Category:Imidazolines Category:Thiazolidines