P-Glycoprotein Deficiency in a Subpopulation of CF-1 Mice Enhances Avermectin-Induced Neurotoxicity

Lankas, George R.; Cartwright, Mark E.; Umbenhauer, Diane R.

doi:10.1006/taap.1996.8086

Cited by 184 publications

(118 citation statements)

References 20 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…ABCB1 polymorphisms may affect the expression and function of P-gp, and variable expression of P-gp can influence the drug disposition in the central nervous system, and thus efficacy. For example, ABCB1 knockout mice show the absence of P-gp in the brain-blood barrier, which causes a higher brain accumulation of ivermectin, resulting in druginduced neurotoxicity [15]. Siddiqui et al [16] demonstrated that the TT genotype at ABCB1 3435 was associated with a better drug response in epilepsy patients.…”

Section: Discussionmentioning

confidence: 99%

Association of ABCB1 polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting

Choi

Lee

et al. 2010

Anaesthesia

View full text Add to dashboard Cite

SummaryWe investigated whether the 2677G>T ⁄ A and 3435C>T polymorphisms of adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) affect the efficacy of ondansetron to prevent postoperative nausea and vomiting. One hundred and ninety-eight patients undergoing general anaesthesia were enrolled. Thirty minutes before the end of surgery, 0.1 mg.kgondansetron was administered intravenously. The incidence of postoperative nausea and vomiting was compared between genotypes in the 2677G>T ⁄ A and 3435C>T polymorphisms of ABCB1. The incidence of postoperative nausea and vomiting was lower in patients with the 2677TT genotype (TT vs Non-TT = 25.9% vs 53.0%, p = 0.01) and 3435TT genotype (CC + CT vs TT = 52.6% vs 21.7%, p = 0.01) during the first 2 h after surgery. There were no significant differences in the incidence of postoperative nausea and vomiting between the different genotype groupings during period between 2 and 24 h after surgery. In conclusion, ABCB1 genotypes may be a clinical predictor of responsiveness for ondansetron. Postoperative nausea and vomiting (PONV) is a common and distressing complication in patients undergoing general anaesthesia. The incidence ranges between 20% and 30%, but is as high as 80% in high-risk patients [1] and may cause significant complications [2]. Although the exact mechanism of PONV is not clear, it is known that the chemoreceptor trigger zone in the area postrema plays an important role, in which the 5-hydroxytryptamine type-3 (5-HT 3 ) receptor is involved in the occurrence of PONV [3].Currently, 5-HT 3 receptor antagonists such as ondansetron are widely used for prevention and treatment of PONV and although these agents have a significant effect, over 35% of patients treated with ondansetron may still experience PONV [4,5]. We hypothesised that polymorphism in the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), an encoding gene of transporter for ondansetron in the brain-blood barrier [6], would contribute to such inter-individual variation.In a previous study, the 3435C>T single nucleotide polymorphism of ABCB1 was associated with the efficacy of 5-HT 3 receptor antagonists for chemotherapy-induced nausea and vomiting [7]. Therefore, we investigated whether the 2677G>T ⁄ A, and 3435C>T polymorphisms of ABCB1 affect the efficacy of ondansetron in preventing PONV in patients undergoing general anaesthesia. MethodsThis study was approved by the Institutional Review Board of Yonsei University Hospital. Written informed consent was obtained from each patient. One hundred and ninety-eight adult patients, of ASA physical status 1-2, undergoing laparoscopic cholecystectomy were enrolled in this study. Patients with a history of drug abuse, known hypersensitivity to 5-HT 3 receptor antagonist, body mass index > 30 kg.m , hepatic or renal disease or who had used antiemetics within the 24 h before the study were excluded. Before surgery, all patients were interviewed about their medical history including tobacco use, presence of PONV and motion sic...

show abstract

Section: Discussionmentioning

confidence: 99%

Association of ABCB1 polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting

Choi

Lee

et al. 2010

Anaesthesia

View full text Add to dashboard Cite

show abstract

“…Ivermectin activates glutamate-gated chloride channels, and the ivermectin cross-resistance of glc 1 flies carrying a mutation in the DmGluCl␣ gene further suggests that this mode of action contributes to ivermectin's insecticidal activity. Ivermectin is widely used to control parasites in humans and animals; however, some cases of ivermectin toxicity have been observed in collies and CF-1 mice, suggesting that ivermectin can act on targets in mammalian brain (31,32). Possible candidates are mammalian GABA-gated and glycine-gated ion channels, the closest mammalian homologues of invertebrate GluCl channels.…”

Section: Discussionmentioning

confidence: 99%

Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin

Kane

Hirschberg

Qian

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

173

146

View full text Add to dashboard Cite

The fruit fly Drosophila melanogaster was used to examine the mode of action of the novel insecticide and acaricide nodulisporic acid. Flies resistant to nodulisporic acid were selected by stepwise increasing the dose of drug in the culture media. The resistant strain, glc 1 , is at least 20-fold resistant to nodulisporic acid and 3-fold cross-resistant to the parasiticide ivermectin, and exhibited decreased brood size, decreased locomotion, and bang sensitivity. Binding assays using glc 1 head membranes showed a marked decrease in the affinity for nodulisporic acid and ivermectin. A combination of genetics and sequencing identified a proline to serine mutation (P299S) in the gene coding for the glutamategated chloride channel subunit DmGluCl␣. To examine the effect of this mutation on the biophysical properties of DmGluCl␣ channels, it was introduced into a recombinant DmGluCl␣, and RNA encoding wild-type and mutant subunits was injected into Xenopus oocytes. Nodulisporic acid directly activated wild-type and mutant DmGluCl␣ channels. However, mutant channels were Ϸ10-fold less sensitive to activation by nodulisporic acid, as well as ivermectin and the endogenous ligand glutamate, providing direct evidence that nodulisporic acid and ivermectin act on DmGluCl␣ channels.

show abstract

“…[115][116] At lower doses, toxicity is observed in animals that lack a functional P-glycoprotein, which allows the drug to accumulate in the nervous system. 117 The role of Pglycoprotein in Loa loa-infected subjects with serious adverse reactions after ivermectin treatment has been investigated. [116][117][118][119][120][121][122] There is also evidence of developmental neurotoxicity (decreased body weight gain, delayed development, intermittent head and whole-body tremors, hind limb extension and then splay) in the F1 offspring of pregnant Sprague Dawley rats treated under controlled conditions with enamectin benzoate, another avermectin pesticide.…”

Section: Parasitesmentioning

confidence: 99%

“…117 The role of Pglycoprotein in Loa loa-infected subjects with serious adverse reactions after ivermectin treatment has been investigated. [116][117][118][119][120][121][122] There is also evidence of developmental neurotoxicity (decreased body weight gain, delayed development, intermittent head and whole-body tremors, hind limb extension and then splay) in the F1 offspring of pregnant Sprague Dawley rats treated under controlled conditions with enamectin benzoate, another avermectin pesticide. 123 Whereas the F0 females showed no abnormal physical signs or deficits in reproductive performance when treated by oral gavage with 0.1-3.6 mg/kg once daily from gestation day 6 to lactation day 20, some pups delivered from the high-dose group developed intermittent head tremors beginning on post-natal day 6 (PND-6).…”

Section: Parasitesmentioning

confidence: 99%

Nodding syndrome in Mundri county, South Sudan: Environmental, nutritional and infectious factors

Spencer¹,

Vandemaele

Richer³

et al. 2013

Afr H. Sci.

View full text Add to dashboard Cite

Background: Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda. Results: Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded. Conclusion: Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food.

show abstract

P-Glycoprotein Deficiency in a Subpopulation of CF-1 Mice Enhances Avermectin-Induced Neurotoxicity

Cited by 184 publications

References 20 publications

Association of ABCB1 polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting

Association of ABCB1 polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting

Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin

Nodding syndrome in Mundri county, South Sudan: Environmental, nutritional and infectious factors

Contact Info

Product

Resources

About