Central and Peripheral Neurotoxic Effects of Ivermectin in Rats
Апстракт
Ivermectin is considered a very safe drug; however, there are reports of toxic effects in particularly sensitive populations or due to accidental overdose. The aim of this study was (1) to further characterize the central and peripheral toxic effects of ivermectin in animals and (2) to determine possible therapeutic strategies for use in cases of ivermectin poisoning. We tested the effects of experimental doses of ivermectin previously reported to cause various intensities of CNS depression. However, in our study, ivermectin at 2.5, 5.0 and 7.5 mg/kg i.v. did not produce visible CNS depression in rats and 10 mg/kg resulted in sleepiness and staggering 10 to 40 min after application, while a dose of 15 mg/kg caused CNS depression very similar to general anesthesia. Ivermectin dose-dependently potentiates thiopentone-induced sleeping time in rats. Flumazenil (0.2 mg/kg), the benzodiazepine antagonist, did not affect the action of thiopentone; however, it significantly reduced sleeping ti...me in rats treated with a combination of ivermectin (10 mg/kg) and thiopentone (25 mg/kg; from 189.86 +/- 45.28 min to 83.13 +/- 32.22 min; mean +/- SD). Ivermectin causes an increase in the tonus (EC50=50.18 mu M) and contraction amplitude (EC50=59.32 mu M) of isolated guinea pig ileum, very similar to GABA, but without the initial relaxation period. These effects are dose-dependent and sensitive to atropine. Our results confirm the central and peripheral GABAergic properties of ivermectin in mammals and also indicate involvement of the cholinergic system in its toxicity. In addition, the results suggest that flumazenil and atropine have potential clinical roles in the treatment of ivermectin toxicity.
Кључне речи:
flumazenil / GABA / isolated ileum / ivermectin / thiopentoneИзвор:
Journal of Veterinary Medical Science, 2011, 73, 5, 591-599Издавач:
- Japan Soc Vet Sci, Tokyo
Финансирање / пројекти:
- Испитивање механизама резистенције и токсичности антихелминтика-ГАБА и никотинских агониста (RS-MESTD-MPN2006-2010-145026)
DOI: 10.1292/jvms.10-0424
ISSN: 0916-7250
PubMed: 21178322
WoS: 000291580300007
Scopus: 2-s2.0-79958042916
Колекције
Институција/група
Fakultet veterinarske medicineTY - JOUR AU - Trailović, Saša AU - Nedeljković-Trailović, Jelena PY - 2011 UR - https://vet-erinar.vet.bg.ac.rs/handle/123456789/788 AB - Ivermectin is considered a very safe drug; however, there are reports of toxic effects in particularly sensitive populations or due to accidental overdose. The aim of this study was (1) to further characterize the central and peripheral toxic effects of ivermectin in animals and (2) to determine possible therapeutic strategies for use in cases of ivermectin poisoning. We tested the effects of experimental doses of ivermectin previously reported to cause various intensities of CNS depression. However, in our study, ivermectin at 2.5, 5.0 and 7.5 mg/kg i.v. did not produce visible CNS depression in rats and 10 mg/kg resulted in sleepiness and staggering 10 to 40 min after application, while a dose of 15 mg/kg caused CNS depression very similar to general anesthesia. Ivermectin dose-dependently potentiates thiopentone-induced sleeping time in rats. Flumazenil (0.2 mg/kg), the benzodiazepine antagonist, did not affect the action of thiopentone; however, it significantly reduced sleeping time in rats treated with a combination of ivermectin (10 mg/kg) and thiopentone (25 mg/kg; from 189.86 +/- 45.28 min to 83.13 +/- 32.22 min; mean +/- SD). Ivermectin causes an increase in the tonus (EC50=50.18 mu M) and contraction amplitude (EC50=59.32 mu M) of isolated guinea pig ileum, very similar to GABA, but without the initial relaxation period. These effects are dose-dependent and sensitive to atropine. Our results confirm the central and peripheral GABAergic properties of ivermectin in mammals and also indicate involvement of the cholinergic system in its toxicity. In addition, the results suggest that flumazenil and atropine have potential clinical roles in the treatment of ivermectin toxicity. PB - Japan Soc Vet Sci, Tokyo T2 - Journal of Veterinary Medical Science T1 - Central and Peripheral Neurotoxic Effects of Ivermectin in Rats VL - 73 IS - 5 SP - 591 EP - 599 DO - 10.1292/jvms.10-0424 ER -
@article{ author = "Trailović, Saša and Nedeljković-Trailović, Jelena", year = "2011", abstract = "Ivermectin is considered a very safe drug; however, there are reports of toxic effects in particularly sensitive populations or due to accidental overdose. The aim of this study was (1) to further characterize the central and peripheral toxic effects of ivermectin in animals and (2) to determine possible therapeutic strategies for use in cases of ivermectin poisoning. We tested the effects of experimental doses of ivermectin previously reported to cause various intensities of CNS depression. However, in our study, ivermectin at 2.5, 5.0 and 7.5 mg/kg i.v. did not produce visible CNS depression in rats and 10 mg/kg resulted in sleepiness and staggering 10 to 40 min after application, while a dose of 15 mg/kg caused CNS depression very similar to general anesthesia. Ivermectin dose-dependently potentiates thiopentone-induced sleeping time in rats. Flumazenil (0.2 mg/kg), the benzodiazepine antagonist, did not affect the action of thiopentone; however, it significantly reduced sleeping time in rats treated with a combination of ivermectin (10 mg/kg) and thiopentone (25 mg/kg; from 189.86 +/- 45.28 min to 83.13 +/- 32.22 min; mean +/- SD). Ivermectin causes an increase in the tonus (EC50=50.18 mu M) and contraction amplitude (EC50=59.32 mu M) of isolated guinea pig ileum, very similar to GABA, but without the initial relaxation period. These effects are dose-dependent and sensitive to atropine. Our results confirm the central and peripheral GABAergic properties of ivermectin in mammals and also indicate involvement of the cholinergic system in its toxicity. In addition, the results suggest that flumazenil and atropine have potential clinical roles in the treatment of ivermectin toxicity.", publisher = "Japan Soc Vet Sci, Tokyo", journal = "Journal of Veterinary Medical Science", title = "Central and Peripheral Neurotoxic Effects of Ivermectin in Rats", volume = "73", number = "5", pages = "591-599", doi = "10.1292/jvms.10-0424" }
Trailović, S.,& Nedeljković-Trailović, J.. (2011). Central and Peripheral Neurotoxic Effects of Ivermectin in Rats. in Journal of Veterinary Medical Science Japan Soc Vet Sci, Tokyo., 73(5), 591-599. https://doi.org/10.1292/jvms.10-0424
Trailović S, Nedeljković-Trailović J. Central and Peripheral Neurotoxic Effects of Ivermectin in Rats. in Journal of Veterinary Medical Science. 2011;73(5):591-599. doi:10.1292/jvms.10-0424 .
Trailović, Saša, Nedeljković-Trailović, Jelena, "Central and Peripheral Neurotoxic Effects of Ivermectin in Rats" in Journal of Veterinary Medical Science, 73, no. 5 (2011):591-599, https://doi.org/10.1292/jvms.10-0424 . .