From the Research
Levamisole acts on helminths primarily by paralyzing the worms through neuromuscular blockade, selectively activating nicotinic acetylcholine receptors on nematode muscle cells, causing sustained muscle contractions, spastic paralysis, and eventual expulsion of the parasites from the host. This mechanism is particularly effective against adult worms rather than larvae. The drug's selectivity comes from its higher affinity for nematode receptors compared to mammalian receptors, providing a reasonable safety margin 1.
Mode of Action
The mode of action of levamisole involves the activation of nicotinic acetylcholine receptors (nAChRs) on the somatic musculature of nematodes, leading to an increase in muscle contraction and eventual paralysis of the worm 2. This is achieved through the binding of levamisole to the nAChR, which opens sodium channels in the muscle cell membranes of nematodes, leading to depolarization and contraction.
Efficacy and Safety
Levamisole is most effective against gastrointestinal nematodes, including Ascaris, hookworms, and some species of Strongyloides 1. The typical dosage for humans is 150 mg as a single oral dose, which may be repeated after 7 days if necessary. For veterinary use, dosages vary by species. However, levamisole has fallen out of favor in human medicine due to potential side effects and the availability of safer alternatives like albendazole and mebendazole, though it remains important in veterinary medicine.
Resistance and Future Directions
Recent studies have shown that there are multiple types of nAChR on the somatic musculature of nematodes, each with different pharmacological properties 2. This has implications for the development of new anthelmintic agents and the potential for increasing the efficacy of existing compounds. Additionally, the modulation of nAChR properties, such as phosphorylation state, may offer a means of increasing the response of a parasite to a fixed concentration of drug.
Key Points
- Levamisole acts on helminths by paralyzing the worms through neuromuscular blockade
- The drug selectively activates nicotinic acetylcholine receptors on nematode muscle cells
- Levamisole is most effective against gastrointestinal nematodes, including Ascaris, hookworms, and some species of Strongyloides
- The typical dosage for humans is 150 mg as a single oral dose, which may be repeated after 7 days if necessary
- Levamisole has fallen out of favor in human medicine due to potential side effects and the availability of safer alternatives.