ArticlePLoS neglected tropical diseases2012
Relative neurotoxicity of ivermectin and moxidectin in Mdr1ab (-/-) mice and effects on mammalian GABA(A) channel activity.
Article in PLoS neglected tropical diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
47 citing papers in PubMed, 79 citations in OpenAlex.
- Synergistic action of piperonyl butoxide with macrocyclic lactones in Rhipicephalus microplus.Experimental & applied acarology · 2026Article
- Interactive effects of ivermectin and nitrogen levels on phytoplankton biomass and stress responses.Ecotoxicology (London, England) · 2026Article
- Efficacy of a novel chewable tablet (Credelio Quattro™) containing lotilaner, moxidectin, praziquantel, and pyrantel for the prevention of heartworm disease (Dirofilaria immitis) in dogs.Parasites & vectors · 2026Article
- Design and Development of Sulfonamide-Chalcones as Antiepileptic Candidates: Computational and Zebrafish-Based Validation Approaches.ACS omega · 2025Article
- Case report: C57BL/6NTac and C57BL/6NCrl mice displaying neurological signs after deworming with ivermectin.Laboratory animals · 2025Article
- Treatment and monitoring of a high-density population of bare-nosed wombats for sarcoptic mange.PloS one · 2025Article
- Moxidectin elevates Candida albicans ergosterol levels to synergize with polyenes against oral candidiasis.Applied microbiology and biotechnology · 2024Article
- A review of moxidectin vs. other macrocyclic lactones for prevention of heartworm disease in dogs with an appraisal of two commercial formulations.Frontiers in veterinary science · 2024Review
- Syringe immersion test asOpen veterinary journal · 2023Article
- Pharmacokinetic and pharmacodynamic considerations for treating sarcoptic mange with cross-relevance to Australian wildlife.International journal for parasitology. Drugs and drug resistance · 2023Review
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- GABAMolecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Ivermectin-Induced Apoptotic Cell Death in Human SH-SY5Y Cells Involves the Activation of Oxidative Stress and Mitochondrial Pathway and Akt/mTOR-Pathway-Mediated Autophagy.Antioxidants (Basel, Switzerland) · 2022Article
- Drug dose and animal welfare: important considerations in the treatment of wildlife.Parasitology research · 2022Article
- Identification and Development of Therapeutics for COVID-19.mSystems · 2021Article
- Drug-based therapeutic strategies for COVID-19-infected patients and their challenges.Future microbiology · 2021Review
- Efficacy of Fenbendazole and Ivermectin againstJournal of the American Association for Laboratory Animal Science : JAALAS · 2021Article
- Metabolism and interactions of Ivermectin with human cytochrome P450 enzymes and drug transporters, possible adverse and toxic effects.Archives of toxicology · 2021Review
- A Novel Dual Drug Approach That Combines Ivermectin and Dihydromyricetin (DHM) to Reduce Alcohol Drinking and Preference in Mice.Molecules (Basel, Switzerland) · 2021Article
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anthelmintics ivermectin (IVM) and moxidectin (MOX) display differences in toxicity in several host species. Entrance into the brain is restricted by the P-glycoprotein (P-gp) efflux transporter, while toxicity is mediated through the brain GABA(A) receptors. This study compared the toxicity of IVM and MOX in vivo and their interaction with GABA(A) receptors in vitro. Drug toxicity was assessed in Mdr1ab(-/-) mice P-gp-deficient after subcutaneous administration of increasing doses (0.11-2.0 and 0.23-12.9 µmol/kg for IVM and MOX in P-gp-deficient mice and half lethal doses (LD(50)) in wild-type mice). Survival was evaluated over 14-days. In Mdr1ab(-/-) mice, LD(50) was 0.46 and 2.3 µmol/kg for IVM and MOX, respectively, demonstrating that MOX was less toxic than IVM. In P-gp-deficient mice, MOX had a lower brain-to-plasma concentration ratio and entered into the brain more slowly than IVM. The brain sublethal drug concentrations determined after administration of doses close to LD(50) were, in Mdr1ab(-/-) and wild-type mice, respectively, 270 and 210 pmol/g for IVM and 830 and 740-1380 pmol/g for MOX, indicating that higher brain concentrations are required for MOX toxicity than IVM. In rat α1β2γ2 GABA channels expressed in Xenopus oocytes, IVM and MOX were both allosteric activators of the GABA-induced response. The Hill coefficient was 1.52±0.45 for IVM and 0.34±0.56 for MOX (p<0.001), while the maximum potentiation caused by IVM and MOX relative to GABA alone was 413.7±66.1 and 257.4±40.6%, respectively (p<0.05), showing that IVM causes a greater potentiation of GABA action on this receptor. Differences in the accumulation of IVM and MOX in the brain and in the interaction of IVM and MOX with GABA(A) receptors account for differences in neurotoxicity seen in intact and Mdr1-deficient animals. These differences in neurotoxicity of IVM and MOX are important in considering their use in humans.
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