Ivermectin effects on motor coordination and contractions of isolated rat diaphragm.
Ivermectin, the antiparasitic drug from the macrocyclic lactones class raises attention due to its high efficiency against nematodes and arthropods and very specific toxic and side effects that it may produce in host. Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality. In our study increasing intravenous doses of ivermectin, (6 or more times higher than therapeutic dose: 1.25, 2.5, 3.75, 5.0, 6.25 and 7.5 mg/kg), caused dose-dependent disturbance of motor coordination in treated rats. The median effective dose (ED50) that was able to impair the rota-rod performance in rats treated 3 min before testing was 2.52 mg/kg. This effect weakens over time, while in the rats treated 60 min before the rota-rod test, ED50 of ivermectin was 4.21 mg/kg. Whereas, all tested doses of ivermectin did not cause any other clinical symptoms of toxicity. Ivermectin has no effect on the contractions of isolated diaphragm caused by the EFS, which effectively blocked mecamylamine (100 μM) and pancuronium (1 and 2 μM). Effect on motor coordination is the first detectable clinical symptom of ivermectin toxicity and apparently is a result of its central effects.
Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, University of Belgrade, Serbia. sasa@vet.bg.ac.rs
Sasa M
SM
Trailovic
Sasa R
SR
Ivanovic
Vladislav M
VM
Varagić
D000818:Animals; D003964:Diaphragm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D044947:Flavonolignans / Q000008:administration & dosage / Q000633:toxicity*; D005730:Ganglionic Blockers / Q000494:pharmacology; D007559:Ivermectin / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D010197:Pancuronium / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D044947:Flavonolignans; D005730:Ganglionic Blockers; D003473:Neuromuscular Nondepolarizing Agents; C556043:anthelminthicol A; D008464:Mecamylamine; D007559:Ivermectin; D010197:Pancuronium