DB00848 - Levamisole
| Identification | |||||||||||
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| Name | Levamisole | ||||||||||
| Accession Number | DB00848 (APRD01067) | ||||||||||
| Type | small molecule | ||||||||||
| 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 |
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| Categories (*) | |||||||||||
| Molecular Weight | 204.291 | ||||||||||
| Groups | approved | ||||||||||
| Monoisotopic Weight | 204.072119084 | ||||||||||
| 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. | ||||||||||
| 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. | ||||||||||
| Protein binding | 20-25% | ||||||||||
| Biotransformation | Primarily hepatic (extensive) with both active and inactive metabolites. | ||||||||||
| Route of elimination | Not Available | ||||||||||
| Toxicity | LD50 = 40 mg/kg (Pigs, subcutaneous); LD50 = 180 mg/kg (rat, oral) | ||||||||||
| Affected organisms |
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| Interactions | |||||||||||
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Targets
| Neuronal acetylcholine receptor subunit alpha-3 | |
|---|---|
| Name | Neuronal acetylcholine receptor subunit alpha-3 |
| Gene Name | CHRNA3 |
| Pharmacological action | yes |
| Actions | agonist |
| References |
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| DTHybrid score | 0.5161 |
| Alkaline phosphatase, placental-like | |
| Name | Alkaline phosphatase, placental-like |
| Gene Name | ALPPL2 |
| Pharmacological action | unknown |
| Actions | inhibitor |
| References |
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| DTHybrid score | 0.7899 |