Banner
targets (2)
for drugs
Identification
Name Levamisole
Accession Number DB00848 (APRD01067)
Type small molecule
Groups approved
Description

An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
dl-Tetramisol
dl-Tetramisole
L-Tetramisole
Levamisol [INN-Spanish]
Levamisole hydrochloride
Levamisolum [INN-Latin]
Phenyl imidothiazole
Salts Not Available
Brand names
Name Company
Ergamisol
Ketrax
Lepuron
Nilverm base
Tetramisol
Tetramisole
Tramisol
Vermisol 150
Wormicid
Brand mixtures Not Available
Categories
  • Antirheumatic Agents
  • Antinematodal Agents
  • Adjuvants, Immunologic
CAS number 14769-73-4
Weight Average: 204.291
Monoisotopic: 204.072119084
Chemical Formula C11H12N2S
InChI Key InChIKey=HLFSDGLLUJUHTE-SNVBAGLBSA-N
InChI
InChI=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
Plain Text
IUPAC Name
(6S)-6-phenyl-2H,3H,5H,6H-imidazo[2,1-b][1,3]thiazole
SMILES
C1CN2C[C@@H](N=C2S1)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenethylamines
Substructures
  • Imidazolines
  • Ureas and Derivatives
  • Benzene and Derivatives
  • Imidazoles
  • Thiazoles
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamidines
  • Thiazolidines
Pharmacology
Indication For adjuvant treatment in combination with fluorouracil after surgical resection in patients with Dukes' stage C colon cancer. Also used to treat malignant melanoma and head/neck cancer. Levamisole was originally used as an antihelminthic to treat worm infestations in both humans and animals.
Pharmacodynamics Levamisole is a synthetic imidazothiazole derivative that has been widely used in treatment of worm infestations in both humans and animals. As an anthelmintic, it probably works by targeting the nematode nicotinergic acetylcholine receptor. As an immunomodulator, it appears that Levamisole is an immunostimulant which has been shown to increase NK cells and activated T-cells in patients receiving this adjuvantly along with 5FU for Stage III colon cancer.
Mechanism of action The mechanism of action of levamisole as an antiparasitic agent appears to be tied to its agnositic activity towards the L-subtype nicotinic acetylcholine receptors in nematode muscles. This agonistic action reduces the capacity of the males to control their reproductive muscles and limits their ability to copulate. The mechanism of action of Levamisole as an anticancer drug in combination with fluorouracil is unknown. The effects of levamisole on the immune system are complex. The drug appears to restore depressed immune function rather than to stimulate response to above-normal levels. Levamisole can stimulate formation of antibodies to various antigens, enhance T-cell responses by stimulating T-cell activation and proliferation, potentiate monocyte and macrophage functions including phagocytosis and chemotaxis, and increase neutrophil mobility, adherence, and chemotaxis.
Absorption Levamisole is rapidly absorbed (2 hours) from the gastrointestinal tract.
Volume of distribution Not Available
Protein binding 20-25%
Metabolism Primarily hepatic (extensive) with both active and inactive metabolites.
Route of elimination Not Available
Half life 4.4-5.6 hours (biphasic)
Clearance Not Available
Toxicity LD50 = 40 mg/kg (Pigs, subcutaneous); LD50 = 180 mg/kg (rat, oral)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Janssen pharmaceutica products lp
Packagers
  • Professional Co.
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Levamisole hcl powder 7.5 USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 264-265 °C Not Available
water solubility 210 mg/mL Not Available
logP 1.84 BIOBYTE (1995)
Predicted Properties
Property Value Source
water solubility 1.44e+00 g/l ALOGPS
logP 2.2 ALOGPS
logP 2.36 ChemAxon
logS -2.1 ALOGPS
pKa (strongest basic) 6.98 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 15.6 ChemAxon
rotatable bond count 1 ChemAxon
refractivity 60.08 ChemAxon
polarizability 22.35 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Grishchenko SV, Lavrukhina LA, Ketiladze ES, Krylov VF, Ershov FI: [Results of combined therapy using levamisole for patients with influenza complicated by pneumonia] Vopr Virusol. 1984 Mar-Apr;29(2):175-9. Pubmed
  2. Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. British Association for Paediatric Nephrology. Lancet. 1991 Jun 29;337(8757):1555-7. Pubmed
  3. Van Belle H: Alkaline phosphatase. I. Kinetics and inhibition by levamisole of purified isoenzymes from humans. Clin Chem. 1976 Jul;22(7):972-6. Pubmed
External Links
Resource Link
KEGG Drug D08114 Link_out
KEGG Compound C07070 Link_out
PubChem Compound 26879 Link_out
PubChem Substance 46509052 Link_out
ChemSpider 25037 Link_out
BindingDB 50241179 Link_out
Therapeutic Targets Database DAP000570 Link_out
PharmGKB PA450205 Link_out
Drug Product Database 645699 Link_out
RxList http://www.rxlist.com/cgi/generic3/levamisole.htm Link_out
Drugs.com http://www.drugs.com/mtm/levamisole.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Levamisole Link_out
ATC Codes
  • P02CE01
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (75.3 KB)
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol Levamisole may increase the anticoagulant effect of acenocoumarol.
Anisindione Levamisole may increase the anticoagulant effect of anisindione.
Dicumarol Levamisole may increase the anticoagulant effect of dicumarol.
Warfarin Levamisole may increase the anticoagulant effect of warfarin.
Food Interactions
  • Take on an empty stomach.
Targets

1. Neuronal acetylcholine receptor subunit alpha-3

Pharmacological action: yes
Actions: agonist

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane

Organism class: human
UniProt ID: P32297 Link_out
Gene: CHRNA3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Culetto E, Baylis HA, Richmond JE, Jones AK, Fleming JT, Squire MD, Lewis JA, Sattelle DB: The Caenorhabditis elegans unc-63 gene encodes a levamisole-sensitive nicotinic acetylcholine receptor alpha subunit. J Biol Chem. 2004 Oct 8;279(41):42476-83. Epub 2004 Jul 27. Pubmed
  4. Rayes D, Flamini M, Hernando G, Bouzat C: Activation of single nicotinic receptor channels from Caenorhabditis elegans muscle. Mol Pharmacol. 2007 May;71(5):1407-15. Epub 2007 Feb 21. Pubmed
  5. Parker S, Peterkin HS, Baylis HA: Muscular dystrophy associated mutations in caveolin-1 induce neurotransmission and locomotion defects in Caenorhabditis elegans. Invert Neurosci. 2007 Sep;7(3):157-64. Epub 2007 Jul 13. Pubmed
  6. Hu Y, Xiao SH, Aroian RV: The new anthelmintic tribendimidine is an L-type (levamisole and pyrantel) nicotinic acetylcholine receptor agonist. PLoS Negl Trop Dis. 2009 Aug 11;3(8):e499. Pubmed
  7. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

2. Alkaline phosphatase, placental-like

Pharmacological action: unknown
Actions: inhibitor

A phosphate monoester + H(2)O = an alcohol + phosphate

Organism class: human
UniProt ID: P10696 Link_out
Gene: ALPPL2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chang YL, Stanford CM, Keller JC: Calcium and phosphate supplementation promotes bone cell mineralization: implications for hydroxyapatite (HA)-enhanced bone formation. J Biomed Mater Res. 2000 Nov;52(2):270-8. Pubmed
  2. Funk CJ: Alkaline phosphatase activity in whitefly salivary glands and saliva. Arch Insect Biochem Physiol. 2001 Apr;46(4):165-74. Pubmed
  3. de Aguiar Matos JA, Borges FP, Tasca T, Bogo MR, De Carli GA, da Graca Fauth M, Dias RD, Bonan CD: Characterisation of an ATP diphosphohydrolase (Apyrase, EC 3.6.1.5) activity in Trichomonas vaginalis. Int J Parasitol. 2001 Jun;31(8):770-5. Pubmed
  4. McDougall K, Plumb C, King WA, Hahnel A: Inhibitor profiles of alkaline phosphatases in bovine preattachment embryos and adult tissues. J Histochem Cytochem. 2002 Mar;50(3):415-22. Pubmed
  5. Soory M, Suchak A: Effects of alkaline phosphatase and its inhibitor levamisole on the modulation of androgen metabolism by nicotine and minocycline in human gingival and oral periosteal fibroblasts. Arch Oral Biol. 2003 Jan;48(1):69-76. Pubmed
  6. Mota A, Silva P, Neves D, Lemos C, Calhau C, Torres D, Martel F, Fraga H, Ribeiro L, Alcada MN, Pinho MJ, Negrao MR, Pedrosa R, Guerreiro S, Guimaraes JT, Azevedo I, Martins MJ: Characterization of rat heart alkaline phosphatase isoenzymes and modulation of activity. Braz J Med Biol Res. 2008 Jul;41(7):600-9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19