Levamisole

Levamisole
Systematic (IUPAC) name
(S)-6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole
Identifiers
CAS number	14769-73-4
ATC code	P02CE01 QP52AE01
PubChem	26879
DrugBank	APRD01067
Chemical data
Formula	C11H12N2S
Mol. mass	204.292 g/mol
Physical data
Density	1.31 g/cm³
Melt. point	61 °C (142 °F)
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic
Half life	4.4-5.6 hours (biphasic)
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	Oral
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Levamisole (marketed as the hydrochloride salt under the trade name Ergamisol) is an antibiotic belonging to a class of synthetic imidazothiazole derivatives. It was discovered at Janssen Pharmaceutica in 1966.

Ergamisol was withdrawn from the U.S. and Canadian markets in 2000 and 2003 respectively.^[1][2]

Clinical use

It was originally used as an antihelminthic to treat worm infestations in both humans and animals. Most commercial preparations are intended for veterinary use as a dewormer for cattle, pigs, and sheep. However, it has also gained prominence among aquarists as an effective treatment for Camallanus roundworm infestations in freshwater tropical fish. ^[3]

It has been tested in combination with fluorouracil to treat colon cancer. There is no good evidence from clinical trials that its addition to fluorouracil therapy benefits patients with colon cancer, and it is no longer used for this. It is also used infrequently to treat melanoma and head and neck cancer. It is unclear from its mechanism of action why it would have an effect in treating colon cancer, although it has been shown to have "immune-stimulating" properties in some situations.

A 1984 study on complicated viral influenza had found levamisole to be an effective interferon inducer and had recommended its use in combination therapy for influenza.^[4]

It is also used routinely in India to treat steroid dependent childhood nephrotic syndrome cases, which is probably based on literature published in a few UK based studies.^[5]

Levamisole has become the subject of recent attention in the medical and public health communities as an alleged new cutting agent in adulterated cocaine. There have been a few cases, first in Canada and then in the United States, of patients with life-threatening infections from agranulocytosis/neutropenia attributed to levamisole-adulterated cocaine.^{[6] [7]} Toxicology reports show that Levamisole, along with Cocaine, were present in DJ AM's body at the time of his death.^[8]

Laboratory use

Levamisole reversibly but uncompetitively inhibits (independent from presence or absence of Mg²⁺) most alkaline phosphatase isoforms (eg human liver, bone, kidney, and spleen) except the intestinal and placental isoform.^[9]

It is thus used as an inhibitor along with substrate to reduce background alkaline phosphatase activity in biomedical research involving detection signal amplification by intestinal alkaline phosphatase for example in in situ hybridization or western blot protocols.

In addition, it is used to immobilize the nematode C. elegans on glass slides for imaging.

Administration and metabolism

Levamisole is given orally, and is metabolized primarily by the liver.

References

1. ^ Frederick, James (November 27, 2000). "Janssen discontinues Ergamisol". Drug Store News. http://findarticles.com/p/articles/mi_m3374/is_18_22/ai_68536218/. Retrieved 2009-08-13. 
2. ^ "Products Discontinued from the Market Since Publication of the 2000 CPS". Canadian Pharmacists Association. http://www.pharmacists.ca/content/hcp/tools/drugnews/discontinued.htm. Retrieved 2009-08-13. 
3. ^ Sanford, Shari (2007). "Levamisole Hydrochloride: Its application and usage in freshwater aquariums". Loaches Online. http://www.loaches.com/disease-treatment/levamisole-hydrochloride-1. Retrieved 2009-02-27. 
4. ^ Grishchenko SV, Lavrukhina LA, Ketiladze ES, Krylov VF, Ershov FI (1984). "[Results of combined therapy using levamisole for patients with influenza complicated by pneumonia]" (in Russian). Vopr. Virusol. 29 (2): 175–9. PMID 6203228. 
5. ^ "Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. British Association for Paediatric Nephrology". Lancet 337 (8757): 1555–7. 1991. PMID 1675705. 
6. ^ Nancy Y Zhu, Donald F. LeGatt, A Robert Turner (February 2009). "Agranulocytosis After Consumption of Cocaine Adulterated With Levamisole". Annals of Internal Medicine 150 (4): 287-289. http://www.annals.org/cgi/content/short/150/4/287. Retrieved 2009-10-7. 
7. ^ Kinzie, Erik (April 2009). "Levamisole Found in Patients Using Cocaine". Annals of Emergency Medicine 53 (4): 546. doi:10.1016/j.annemergmed.2008.10.017. http://www.mdconsult.com/das/article/body/154945316-2/jorg=journal&source=&sp=21877276&sid=0/N/691072/1.html?issn=01960644. Retrieved 2009-08-18. 
8. ^ http://www.sfgate.com/cgi-bin/article.cgi?f=/n/a/2009/09/29/national/a075802D66.DTL&tsp=1
9. ^ Van Belle H (1976). "Alkaline phosphatase. I. Kinetics and inhibition by levamisole of purified isoenzymes from humans". Clin. Chem. 22 (7): 972–6. PMID 6169. 

External links

• http://www.vectorlabs.com/Protocols/Substrates/SP5000.pdf

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