Ivermectin

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Chick and human alpha7 nicotinic acetylcholine receptors in Xenopus laevis oocytes and K-28 cells

exposure

Micromolar ivermectin preapplication

limitations

Micromolar exposure in a heterologous expression system is well above ordinary antiparasitic plasma concentrations, and the authors exclude a nonspecific chloride current rather than establishing an in vivo effect.

organism

Chick and human alpha7 nicotinic acetylcholine receptors in Xenopus laevis oocytes and K-28 cells

plain_language

Preapplication of ivermectin in the micromolar range strongly enhanced the acetylcholine-evoked current of alpha7 nicotinic acetylcholine receptors, acting as a positive allosteric effector.

primary_references

Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor. (1998). https://pubmed.ncbi.nlm.nih.gov/9463487/ DOI: 10.1124/mol.53.2.283

route

In vitro

tissue

Ligand-gated cation channel current

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 79–88

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-alpha7-nicotinic-potentiation Preapplication of ivermectin in the micromolar range strongly enhanced the acetylcholine-evoked current of alpha7 nicotinic acetylcholine receptors, acting as a positive allosteric effector. Model/species: Chick and human alpha7 nicotinic acetylcholine receptors in Xenopus laevis oocytes and K-28 cells Tissue/system: Ligand-gated cation channel current Exposure: Micromolar ivermectin preapplication Route: In vitro Duration: Acute Limits: Micromolar exposure in a heterologous expression system is well above ordinary antiparasitic plasma concentrations, and the authors exclude a nonspecific chloride current rather than establishing an in vivo effect. Primary reference: Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor. (1998). https://pubmed.ncbi.nlm.nih.gov/9463487/ DOI: 10.1124/mol.53.2.283 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Brugia malayi microfilariae

exposure

Ivermectin in vitro

limitations

The link from reduced secretion to rapid microfilarial clearance in the host is proposed by the authors, not measured in this work.

organism

Brugia malayi microfilariae

plain_language

Ivermectin exposure decreased the amount of protein released from the excretory-secretory apparatus of Brugia malayi microfilariae.

primary_references

Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. (2010). https://pubmed.ncbi.nlm.nih.gov/21041637/ DOI: 10.1073/pnas.1011983107

route

In vitro

tissue

Excretory-secretory vesicle and the muscle structure surrounding it, where GluCl expression was localised

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 35–44

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-es-protein-release Ivermectin exposure decreased the amount of protein released from the excretory-secretory apparatus of Brugia malayi microfilariae. Model/species: Brugia malayi microfilariae Tissue/system: Excretory-secretory vesicle and the muscle structure surrounding it, where GluCl expression was localised Exposure: Ivermectin in vitro Route: In vitro Duration: Acute Limits: The link from reduced secretion to rapid microfilarial clearance in the host is proposed by the authors, not measured in this work. Primary reference: Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. (2010). https://pubmed.ncbi.nlm.nih.gov/21041637/ DOI: 10.1073/pnas.1011983107 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not applicable

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

High-throughput compound library screen, FXR ligand-binding domain crystal structure

exposure

Ivermectin complexed with the FXR ligand-binding domain

limitations

The authors describe FXR as the first mammalian protein targeted by ivermectin with high selectivity, which is a claim about selectivity among mammalian targets rather than about potency.

organism

High-throughput compound library screen, FXR ligand-binding domain crystal structure

plain_language

Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket.

primary_references

The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924

route

In vitro and structural

tissue

Nuclear receptor transcriptional activity and coregulator recruitment

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 123–132

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-fxr-ligand Ivermectin bound the farnesoid X receptor ligand-binding domain and induced its transcriptional activity, with a crystal structure showing a distinct binding mode and an expanded ligand-binding pocket. Model/species: High-throughput compound library screen, FXR ligand-binding domain crystal structure Tissue/system: Nuclear receptor transcriptional activity and coregulator recruitment Exposure: Ivermectin complexed with the FXR ligand-binding domain Route: In vitro and structural Duration: Not applicable Limits: The authors describe FXR as the first mammalian protein targeted by ivermectin with high selectivity, which is a claim about selectivity among mammalian targets rather than about potency. Primary reference: The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not applicable

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Homopentameric Caenorhabditis elegans GluCl alpha, X-ray structure at 3.3 angstrom resolution

exposure

GluCl-Fab complex determined with ivermectin as allosteric agonist, and separately with L-glutamate and picrotoxin

limitations

A structure establishes a binding site and a stabilised conformation; it does not establish the concentration at which this occurs in a living parasite.

organism

Homopentameric Caenorhabditis elegans GluCl alpha, X-ray structure at 3.3 angstrom resolution

plain_language

Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation.

primary_references

Principles of activation and permeation in an anion-selective Cys-loop receptor. (2011). https://pubmed.ncbi.nlm.nih.gov/21572436/ DOI: 10.1038/nature10139

route

Structural

tissue

Anion-selective Cys-loop receptor gating and permeation

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 24–33

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-glucl-open-pore Ivermectin binds in the transmembrane domain of the Caenorhabditis elegans glutamate-gated chloride channel and stabilises an open-pore conformation. Model/species: Homopentameric Caenorhabditis elegans GluCl alpha, X-ray structure at 3.3 angstrom resolution Tissue/system: Anion-selective Cys-loop receptor gating and permeation Exposure: GluCl-Fab complex determined with ivermectin as allosteric agonist, and separately with L-glutamate and picrotoxin Route: Structural Duration: Not applicable Limits: A structure establishes a binding site and a stabilised conformation; it does not establish the concentration at which this occurs in a living parasite. Primary reference: Principles of activation and permeation in an anion-selective Cys-loop receptor. (2011). https://pubmed.ncbi.nlm.nih.gov/21572436/ DOI: 10.1038/nature10139 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Acute and irreversible within the experiment

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Recombinant human alpha1 homomeric and alpha1beta heteromeric glycine receptors

exposure

0.03 micromolar potentiation and higher-concentration irreversible activation

limitations

Ivermectin-gated currents showed markedly reduced sensitivity to strychnine, picrotoxin and zinc, so the pharmacology of this activation differs from ordinary glycinergic transmission.

organism

Recombinant human alpha1 homomeric and alpha1beta heteromeric glycine receptors

plain_language

Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site.

primary_references

Ivermectin, an unconventional agonist of the glycine receptor chloride channel. (2001). https://pubmed.ncbi.nlm.nih.gov/11278873/ DOI: 10.1074/jbc.M011264200

route

In vitro

tissue

Inhibitory chloride channel gating

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 112–121

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-glycine-receptor-activation Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site. Model/species: Recombinant human alpha1 homomeric and alpha1beta heteromeric glycine receptors Tissue/system: Inhibitory chloride channel gating Exposure: 0.03 micromolar potentiation and higher-concentration irreversible activation Route: In vitro Duration: Acute and irreversible within the experiment Limits: Ivermectin-gated currents showed markedly reduced sensitivity to strychnine, picrotoxin and zinc, so the pharmacology of this activation differs from ordinary glycinergic transmission. Primary reference: Ivermectin, an unconventional agonist of the glycine receptor chloride channel. (2001). https://pubmed.ncbi.nlm.nih.gov/11278873/ DOI: 10.1074/jbc.M011264200 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

HIV-1 and dengue virus replication assays

exposure

Ivermectin

limitations

Antiviral activity in culture is attributed to the import mechanism by inference from the known import dependence of these viral proteins.

organism

HIV-1 and dengue virus replication assays

plain_language

Ivermectin inhibited replication of HIV-1 and dengue virus, both of which depend on importin alpha/beta nuclear import of HIV-1 integrase and dengue NS5 polymerase respectively.

primary_references

Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. (2012). https://pubmed.ncbi.nlm.nih.gov/22417684/ DOI: 10.1042/BJ20120150

route

In vitro

tissue

Viral protein nuclear import

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 156–165

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-hiv-dengue-replication Ivermectin inhibited replication of HIV-1 and dengue virus, both of which depend on importin alpha/beta nuclear import of HIV-1 integrase and dengue NS5 polymerase respectively. Model/species: HIV-1 and dengue virus replication assays Tissue/system: Viral protein nuclear import Exposure: Ivermectin Route: In vitro Duration: Not stated here Limits: Antiviral activity in culture is attributed to the import mechanism by inference from the known import dependence of these viral proteins. Primary reference: Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. (2012). https://pubmed.ncbi.nlm.nih.gov/22417684/ DOI: 10.1042/BJ20120150 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Nuclear transport assays following a high-throughput screen

exposure

Ivermectin

limitations

Specificity here is specificity among import pathways; the concentration required is not stated in the abstract.

organism

Nuclear transport assays following a high-throughput screen

plain_language

Ivermectin inhibited importin alpha/beta-mediated nuclear import broadly, with no effect on a range of other nuclear import pathways including import mediated by importin beta1 alone.

primary_references

Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. (2012). https://pubmed.ncbi.nlm.nih.gov/22417684/ DOI: 10.1042/BJ20120150

route

In vitro

tissue

Protein movement between cytoplasm and nucleus

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 145–154

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-importin-nuclear-import Ivermectin inhibited importin alpha/beta-mediated nuclear import broadly, with no effect on a range of other nuclear import pathways including import mediated by importin beta1 alone. Model/species: Nuclear transport assays following a high-throughput screen Tissue/system: Protein movement between cytoplasm and nucleus Exposure: Ivermectin Route: In vitro Duration: Acute Limits: Specificity here is specificity among import pathways; the concentration required is not stated in the abstract. Primary reference: Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. (2012). https://pubmed.ncbi.nlm.nih.gov/22417684/ DOI: 10.1042/BJ20120150 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Acute myeloid leukemia cell lines and primary patient samples

exposure

Low micromolar ivermectin

limitations

The mitochondrial membrane potential was explicitly unchanged, which separates this from mechanisms that act through mitochondrial depolarisation.

organism

Acute myeloid leukemia cell lines and primary patient samples

plain_language

Ivermectin increased intracellular chloride concentration and cell size in leukemia cells, accompanied by plasma membrane hyperpolarisation without a change in mitochondrial membrane potential.

primary_references

The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. (2010). https://pubmed.ncbi.nlm.nih.gov/20644115/ DOI: 10.1182/blood-2010-01-262675

route

In vitro

tissue

Chloride flux and membrane potential

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 178–187

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-leukemia-chloride-influx Ivermectin increased intracellular chloride concentration and cell size in leukemia cells, accompanied by plasma membrane hyperpolarisation without a change in mitochondrial membrane potential. Model/species: Acute myeloid leukemia cell lines and primary patient samples Tissue/system: Chloride flux and membrane potential Exposure: Low micromolar ivermectin Route: In vitro Duration: Not stated here Limits: The mitochondrial membrane potential was explicitly unchanged, which separates this from mechanisms that act through mitochondrial depolarisation. Primary reference: The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. (2010). https://pubmed.ncbi.nlm.nih.gov/20644115/ DOI: 10.1182/blood-2010-01-262675 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Acute myeloid leukemia cell lines and primary patient samples, with three mouse leukemia models

exposure

Low micromolar ivermectin; mouse dosing described as appearing pharmacologically achievable

limitations

Death was preferential for leukemia cells over normal hematopoietic cells rather than exclusive to them, and synergy was reported with cytarabine and daunorubicin, which also raise reactive oxygen species.

organism

Acute myeloid leukemia cell lines and primary patient samples, with three mouse leukemia models

plain_language

Ivermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death.

primary_references

The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. (2010). https://pubmed.ncbi.nlm.nih.gov/20644115/ DOI: 10.1182/blood-2010-01-262675

route

In vitro and in vivo

tissue

Reactive oxygen species and cell viability

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 189–198

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-leukemia-reactive-oxygen Ivermectin increased reactive oxygen species generation in leukemia cells, and that increase was functionally required for ivermectin-induced cell death. Model/species: Acute myeloid leukemia cell lines and primary patient samples, with three mouse leukemia models Tissue/system: Reactive oxygen species and cell viability Exposure: Low micromolar ivermectin; mouse dosing described as appearing pharmacologically achievable Route: In vitro and in vivo Duration: Not stated here Limits: Death was preferential for leukemia cells over normal hematopoietic cells rather than exclusive to them, and synergy was reported with cytarabine and daunorubicin, which also raise reactive oxygen species. Primary reference: The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells. (2010). https://pubmed.ncbi.nlm.nih.gov/20644115/ DOI: 10.1182/blood-2010-01-262675 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Wild-type and FXR-null mice

exposure

Ivermectin treatment

limitations

The null-mouse comparison attributes the metabolic effect to FXR; it does not establish a dose relevant to human antiparasitic use.

organism

Wild-type and FXR-null mice

plain_language

Ivermectin decreased serum glucose and cholesterol in wild-type mice but not in FXR-null mice.

primary_references

The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924

route

In vivo

tissue

Serum glucose and cholesterol

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 134–143

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-lowers-glucose-through-fxr Ivermectin decreased serum glucose and cholesterol in wild-type mice but not in FXR-null mice. Model/species: Wild-type and FXR-null mice Tissue/system: Serum glucose and cholesterol Exposure: Ivermectin treatment Route: In vivo Duration: Not stated here Limits: The null-mouse comparison attributes the metabolic effect to FXR; it does not establish a dose relevant to human antiparasitic use. Primary reference: The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Brugia malayi microfilariae in culture

exposure

Pharmacologically relevant ivermectin concentrations

limitations

A null result in culture does not exclude killing in the host, where immune clearance is available; it is the reason the secretion mechanism was investigated.

organism

Brugia malayi microfilariae in culture

plain_language

Ivermectin had little direct effect on Brugia malayi microfilariae in culture at pharmacologically relevant concentrations.

primary_references

Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. (2010). https://pubmed.ncbi.nlm.nih.gov/21041637/ DOI: 10.1073/pnas.1011983107

route

In vitro

tissue

Parasite viability

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 46–55

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-microfilaria-direct-kill-null Ivermectin had little direct effect on Brugia malayi microfilariae in culture at pharmacologically relevant concentrations. Model/species: Brugia malayi microfilariae in culture Tissue/system: Parasite viability Exposure: Pharmacologically relevant ivermectin concentrations Route: In vitro Duration: Not stated here Limits: A null result in culture does not exclude killing in the host, where immune clearance is available; it is the reason the secretion mechanism was investigated. Primary reference: Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. (2010). https://pubmed.ncbi.nlm.nih.gov/21041637/ DOI: 10.1073/pnas.1011983107 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Adult rat trigeminal mesencephalic nucleus and hippocampal CA1 neurons

exposure

Ivermectin at concentrations that modulated heterologously expressed P2X4

limitations

The authors read this as evidence that homomeric P2X4 is not the primary P2X subtype in these neurons, not as evidence that ivermectin fails to reach the channel.

organism

Adult rat trigeminal mesencephalic nucleus and hippocampal CA1 neurons

plain_language

Ivermectin produced no significant effect on fast ATP-evoked inward currents in adult trigeminal mesencephalic nucleus or hippocampal CA1 neurons.

primary_references

Allosteric control of gating and kinetics at P2X(4) receptor channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10460235/ DOI: 10.1523/JNEUROSCI.19-17-07289.1999

route

In vitro

tissue

Endogenously expressed P2X receptor currents

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 101–110

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-native-p2x-current-null Ivermectin produced no significant effect on fast ATP-evoked inward currents in adult trigeminal mesencephalic nucleus or hippocampal CA1 neurons. Model/species: Adult rat trigeminal mesencephalic nucleus and hippocampal CA1 neurons Tissue/system: Endogenously expressed P2X receptor currents Exposure: Ivermectin at concentrations that modulated heterologously expressed P2X4 Route: In vitro Duration: Acute Limits: The authors read this as evidence that homomeric P2X4 is not the primary P2X subtype in these neurons, not as evidence that ivermectin fails to reach the channel. Primary reference: Allosteric control of gating and kinetics at P2X(4) receptor channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10460235/ DOI: 10.1523/JNEUROSCI.19-17-07289.1999 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Heterologously expressed P2X4 and P2X4/P2X6 channels

exposure

Submicromolar ivermectin, rapid and reversible

limitations

The effect was specific to P2X4 and absent at P2X2, P2X3, P2X2/P2X3 and P2X7, so it cannot be generalised to ATP signalling as a whole.

organism

Heterologously expressed P2X4 and P2X4/P2X6 channels

plain_language

Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation.

primary_references

Allosteric control of gating and kinetics at P2X(4) receptor channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10460235/ DOI: 10.1523/JNEUROSCI.19-17-07289.1999

route

In vitro

tissue

ATP-gated cation channel gating and kinetics

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 90–99

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-p2x4-potentiation Ivermectin was a specific positive allosteric effector of heterologously expressed P2X4 channels with an EC50 near 250 nanomolar, increasing current amplitude and slowing deactivation. Model/species: Heterologously expressed P2X4 and P2X4/P2X6 channels Tissue/system: ATP-gated cation channel gating and kinetics Exposure: Submicromolar ivermectin, rapid and reversible Route: In vitro Duration: Acute Limits: The effect was specific to P2X4 and absent at P2X2, P2X3, P2X2/P2X3 and P2X7, so it cannot be generalised to ATP signalling as a whole. Primary reference: Allosteric control of gating and kinetics at P2X(4) receptor channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10460235/ DOI: 10.1523/JNEUROSCI.19-17-07289.1999 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human breast cancer cells and breast cancer xenografts

exposure

Ivermectin

limitations

The autophagy described is cytostatic and associated with suppressed tumour growth rather than cytotoxic killing.

organism

Human breast cancer cells and breast cancer xenografts

plain_language

Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells.

primary_references

Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. (2016). https://pubmed.ncbi.nlm.nih.gov/27302166/ DOI: 10.1158/0008-5472.CAN-15-2887

route

In vitro and in vivo xenograft

tissue

PAK1 abundance, Akt phosphorylation and autophagy

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 211–220

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-pak1-akt-autophagy Ivermectin decreased PAK1 through ubiquitination-mediated degradation, lowering Akt phosphorylation and blocking Akt/mTOR signalling, which produced cytostatic autophagy in breast cancer cells. Model/species: Human breast cancer cells and breast cancer xenografts Tissue/system: PAK1 abundance, Akt phosphorylation and autophagy Exposure: Ivermectin Route: In vitro and in vivo xenograft Duration: Not stated here Limits: The autophagy described is cytostatic and associated with suppressed tumour growth rather than cytotoxic killing. Primary reference: Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. (2016). https://pubmed.ncbi.nlm.nih.gov/27302166/ DOI: 10.1158/0008-5472.CAN-15-2887 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

12 weeks, with extension to 36 weeks for relapse

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Humans with moderate-to-severe papulopustular rosacea

exposure

Topical ivermectin 1% cream

limitations

Relapse after discontinuation was common in both arms, 62.7% with ivermectin and 68.4% with metronidazole by week 36, and ivermectin has only been tested in moderate-to-severe disease.

organism

Humans with moderate-to-severe papulopustular rosacea

plain_language

Topical ivermectin 1% cream was an effective treatment for moderate-to-severe papulopustular rosacea and was more effective than topical metronidazole at twelve weeks, with a number needed to treat of 10.5.

primary_references

Topical Ivermectin in the Treatment of Papulopustular Rosacea: A Systematic Review of Evidence and Clinical Guideline Recommendations. (2018). https://pubmed.ncbi.nlm.nih.gov/29943217/ DOI: 10.1007/s13555-018-0249-y

route

Topical

tissue

Inflammatory facial lesions, with acaricidal activity against Demodex mites

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 233–242

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-rosacea-lesions Topical ivermectin 1% cream was an effective treatment for moderate-to-severe papulopustular rosacea and was more effective than topical metronidazole at twelve weeks, with a number needed to treat of 10.5. Model/species: Humans with moderate-to-severe papulopustular rosacea Tissue/system: Inflammatory facial lesions, with acaricidal activity against Demodex mites Exposure: Topical ivermectin 1% cream Route: Topical Duration: 12 weeks, with extension to 36 weeks for relapse Limits: Relapse after discontinuation was common in both arms, 62.7% with ivermectin and 68.4% with metronidazole by week 36, and ivermectin has only been tested in moderate-to-severe disease. Primary reference: Topical Ivermectin in the Treatment of Papulopustular Rosacea: A Systematic Review of Evidence and Clinical Guideline Recommendations. (2018). https://pubmed.ncbi.nlm.nih.gov/29943217/ DOI: 10.1007/s13555-018-0249-y Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

48 hours

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Vero-hSLAM cell culture

exposure

Single ivermectin addition two hours post infection

limitations

This is a cell-culture result in a monkey kidney line, and the authors state only that it warrants further investigation for possible benefits in humans. The concentration relationship to human plasma exposure is not addressed in the report and remains unresolved here.

organism

Vero-hSLAM cell culture

plain_language

A single addition of ivermectin to SARS-CoV-2-infected Vero-hSLAM cells two hours after infection produced approximately a five thousand fold reduction in viral RNA at forty-eight hours.

primary_references

The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. (2020). https://pubmed.ncbi.nlm.nih.gov/32251768/ DOI: 10.1016/j.antiviral.2020.104787

route

In vitro

tissue

Viral RNA

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 167–176

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-sars-cov-2-cell-culture A single addition of ivermectin to SARS-CoV-2-infected Vero-hSLAM cells two hours after infection produced approximately a five thousand fold reduction in viral RNA at forty-eight hours. Model/species: Vero-hSLAM cell culture Tissue/system: Viral RNA Exposure: Single ivermectin addition two hours post infection Route: In vitro Duration: 48 hours Limits: This is a cell-culture result in a monkey kidney line, and the authors state only that it warrants further investigation for possible benefits in humans. The concentration relationship to human plasma exposure is not addressed in the report and remains unresolved here. Primary reference: The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. (2020). https://pubmed.ncbi.nlm.nih.gov/32251768/ DOI: 10.1016/j.antiviral.2020.104787 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human cancer cell lines and xenografts

exposure

Ivermectin, with low-concentration effects rescued by direct activation with TCF-VP16

limitations

In vivo inhibition was selective for TCF-dependent xenografts and absent in TCF-independent ones, which supports pathway specificity but does not establish the molecular binding partner.

organism

Human cancer cell lines and xenografts

plain_language

Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved.

primary_references

The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. (2014). https://pubmed.ncbi.nlm.nih.gov/25143352/ DOI: 10.15252/emmm.201404084

route

In vitro and in vivo xenograft

tissue

Canonical WNT-TCF signalling output

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 200–209

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-wnt-tcf-blockade Ivermectin inhibited the expression of WNT-TCF target genes and repressed C-terminal beta-catenin phosphoforms and CYCLIN D1 in a manner sensitive to okadaic acid, indicating that protein phosphatases are involved. Model/species: Human cancer cell lines and xenografts Tissue/system: Canonical WNT-TCF signalling output Exposure: Ivermectin, with low-concentration effects rescued by direct activation with TCF-VP16 Route: In vitro and in vivo xenograft Duration: Not stated here Limits: In vivo inhibition was selective for TCF-dependent xenografts and absent in TCF-independent ones, which supports pathway specificity but does not establish the molecular binding partner. Primary reference: The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. (2014). https://pubmed.ncbi.nlm.nih.gov/25143352/ DOI: 10.15252/emmm.201404084 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

mdr1a,b double knockout mice and bcrp knockout mice, against wild type

exposure

Ivermectin 0.2 mg/kg and selamectin 12 mg/kg, intravenous, oral and dermal spot-on

limitations

Breast cancer resistance protein knockouts showed no difference, so this margin is specific to P-glycoprotein and not to efflux transport in general.

organism

mdr1a,b double knockout mice and bcrp knockout mice, against wild type

plain_language

Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold.

primary_references

Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19161460/ DOI: 10.1111/j.1365-2885.2008.01007.x

route

In vivo

tissue

Brain penetration, organ distribution and plasma kinetics

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 68–77

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-brain-accumulation-without-pgp Ivermectin accumulated thirty-six to sixty fold in the brain of mdr1a,b knockout mice compared with wild type, while selamectin accumulated only five to ten fold. Model/species: mdr1a,b double knockout mice and bcrp knockout mice, against wild type Tissue/system: Brain penetration, organ distribution and plasma kinetics Exposure: Ivermectin 0.2 mg/kg and selamectin 12 mg/kg, intravenous, oral and dermal spot-on Route: In vivo Duration: Not stated here Limits: Breast cancer resistance protein knockouts showed no difference, so this margin is specific to P-glycoprotein and not to efflux transport in general. Primary reference: Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19161460/ DOI: 10.1111/j.1365-2885.2008.01007.x Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Caenorhabditis elegans complementary DNAs expressed in Xenopus oocytes

exposure

Avermectin applied to the expressed channel

limitations

The same report notes that avermectins also interact with vertebrate and invertebrate GABA receptors, so an invertebrate-only target cannot be inferred from this channel alone.

organism

Caenorhabditis elegans complementary DNAs expressed in Xenopus oocytes

plain_language

An avermectin-sensitive glutamate-gated chloride channel was cloned from Caenorhabditis elegans and shown to be a new member of the ligand-gated ion channel superfamily.

primary_references

Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. (1994). https://pubmed.ncbi.nlm.nih.gov/7935817/ DOI: 10.1038/371707a0

route

In vitro

tissue

Expression cloning and electrophysiology of a glutamate-gated chloride channel

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 13–22

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## ivermectin-glucl-cloning An avermectin-sensitive glutamate-gated chloride channel was cloned from Caenorhabditis elegans and shown to be a new member of the ligand-gated ion channel superfamily. Model/species: Caenorhabditis elegans complementary DNAs expressed in Xenopus oocytes Tissue/system: Expression cloning and electrophysiology of a glutamate-gated chloride channel Exposure: Avermectin applied to the expressed channel Route: In vitro Duration: Acute Limits: The same report notes that avermectins also interact with vertebrate and invertebrate GABA receptors, so an invertebrate-only target cannot be inferred from this channel alone. Primary reference: Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. (1994). https://pubmed.ncbi.nlm.nih.gov/7935817/ DOI: 10.1038/371707a0 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

mdr1a homozygous knockout mice compared with wild type

exposure

Ivermectin, described in this report as a centrally neurotoxic pesticide

limitations

The comparison is a complete gene disruption, which is a stronger manipulation than partial pharmacological inhibition of P-glycoprotein.

organism

mdr1a homozygous knockout mice compared with wild type

plain_language

Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.

primary_references

Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. (1994). https://pubmed.ncbi.nlm.nih.gov/7910522/ DOI: 10.1016/0092-8674(94)90212-7

route

In vivo

tissue

Blood-brain barrier and tissue drug distribution

Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 57–66

Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## pgp-restricts-ivermectin-brain-entry Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier. Model/species: mdr1a homozygous knockout mice compared with wild type Tissue/system: Blood-brain barrier and tissue drug distribution Exposure: Ivermectin, described in this report as a centrally neurotoxic pesticide Route: In vivo Duration: Not stated here Limits: The comparison is a complete gene disruption, which is a stronger manipulation than partial pharmacological inhibition of P-glycoprotein. Primary reference: Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. (1994). https://pubmed.ncbi.nlm.nih.gov/7910522/ DOI: 10.1016/0092-8674(94)90212-7 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.