[Pharmacological effects of ivermectin, an antiparasitic agent for intestinal strongyloidiasis: its mode of action and clinical efficacy].
Abstract: Ivermectin is an oral semi-synthetic lactone anthelmintic agent derived from avermectins isolated from fermentation products of Streptomyces avermitilis. Ivermectin showed a concentration-dependent inhibitory effect on motility of a free-living nematode, Caenorhabditis elegans (C. elegans). There exist specific binding sites having a high affinity for ivermectin in the membrane fraction of C. elegans, and a strong positive correlation was detected between the affinity for these binding sites and the suppressive effect on motility of C. elegans in several ivermectin-related substances. These results suggested that the binding to these binding sites is important for the nematocidal activity of ivermectin. In oocytes of Xenopus laevis injected with the Poly (A)(+) RNA of C. elegans, expression of a chloride channel, which is irreversibly activated by ivermectin, was recognized. The pharmacological properties of this channel suggest that the ivermectin-sensitive channel is a glutamate-activated chloride channel. As to the glutamate-activated chloride channel, two subtypes (GluCl-alpha and GluCl-beta) were cloned, suggesting these subtypes constitute the glutamate-activated chloride channel. These findings suggest that ivermectin binds to glutamate-activated chloride channels existing in nerve or muscle cells of nematode with a specific and high affinity, causing hyperpolarization of nerve or muscle cells by increasing permeability of chloride ion through the cell membrane, and as a result, the parasites are paralyzed to death. In experimental infections in sheep and cattle, ivermectin exhibited potent dose-dependent anthelmintic effects on Haemonchus, Ostertagia, Trichostrongylus, Cooperia, Oesphagostomum, and Dictyocaulus. Anthelmintic effects were reported also in dogs, horses, and humans infected with Strongyloides. In the clinical Phase III trial in Japan, 50 patients infected with Strongyloides stercoralis were administered approx. 200 microg/kg of ivermectin to be given orally twice at an interval of 2 weeks. As a result, the Strongyloides stercoralis-eradicating rate was 98.0% (49/50).
Publication Date: 2003-11-26 PubMed ID: 14639007DOI: 10.1254/fpj.122.527Google Scholar: Lookup
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Summary
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The study explores the pharmacological effects and clinical efficacy of ivermectin, a medication used for treating parasitic infections in humans and animals. The research indicates how the drug operates, its specific targeting mechanisms, and its successful application in various clinical trials.
Experimental Findings
- The researchers claim that ivermectin, a semi-synthetic drug developed from substances derived from the Streptomyces avermitilis bacteria, influence the motility of a type of nematode (C. elegans). The effect was found to be concentration-dependent, meaning the more ivermectin present, the greater the impact on the nematode’s movement.
- Ivermectin’s action appears to be linked to specific binding sites in the nematode, suggesting the drug operates by attaching to these points. The higher the compatibility of ivermectin and these sites, the greater the suppression of the nematode’s motility.
Channel Activation
- This study unearthed a link between ivermectin and the activation of a specific chloride channel. When oocytes (immature eggs) of Xenopus laevis were injected with RNA of C. elegans, a chloride channel that responds to ivermectin was activated permanently, suggesting that the drug works by changing the function of this channel.
- The researchers further discovered that the channel in question resembled a glutamate-activated chloride channel, implying that ivermectin’s effects relate to this particular channel type.
- Interestingly, two subtypes of this channel were cloned, hinting at the possibility of varied approaches to its regulation and action by ivermectin.
Parasitic Death
- The drug harbors potential anti-parasitic properties by targeting the glutamate-activated chloride channels in the nerve or muscle cells of the parasite. Increased permeability of chloride ions through the cell membrane leads to hyperpolarization (an increase in the cell’s charge) and ultimately paralyzes the parasite, leading to its death.
Anthelmintic Effects and Clinical Trials
- Ivermectin’s potency in treating parasitic infections was demonstrated through several trials on sheep, cattle, horses, dogs, and humans suffering from Strongyloides worms.
- In a clinical trial in Japan, ivermectin proved highly effective in relieving patients from Strongyloides stercoralis, a type of nematode; 98.0% of patients showed a significant reduction in the parasitic population after taking a specific dosage of the drug.
Cite This Article
APA
Ikeda T.
(2003).
[Pharmacological effects of ivermectin, an antiparasitic agent for intestinal strongyloidiasis: its mode of action and clinical efficacy].
Nihon Yakurigaku Zasshi, 122(6), 527-538.
https://doi.org/10.1254/fpj.122.527 Publication
Researcher Affiliations
- Safety Assessment, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan.
MeSH Terms
- Animals
- Anthelmintics / metabolism
- Anthelmintics / pharmacology
- Caenorhabditis elegans / drug effects
- Cattle
- Chloride Channels / metabolism
- Dogs
- Horses
- Humans
- Ivermectin / metabolism
- Ivermectin / pharmacology
- Sheep
- Strongyloidiasis / drug therapy
- Strongyloidiasis / parasitology
Citations
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