title: The effect of ivermectin on convulsions in rats produced by lidocaine and strychnine.
abstract: Ivermectin is one of the most commonly used drugs in pharmacotherapy of parasitic diseases in domestic and wild animals caused by parasitic nematodes and arthropods. However, ivermectin and other avermectins very often produce side-effects in hosts. The most dominant clinical symptom of ivermectin toxicity in domestic and wild animals is CNS depression. In nematodes, the target site of ivermectin's action is glutamate-gated chloride-channel receptor and GABA receptor. The depressive effect of ivermectin in mammals might include more than one mechanism; therefore, the anticonvulsive effect of ivermectin against convulsions caused by lidocaine and strychnine was evaluated. Ivermectin antagonized lidocaine- and strychnine-induced convulsions in rats, although these have different mechanisms. In the present study, the anticonvulsive ED50 ofivermectin for lidocaine-induced convulsions was 2.44 mg/kg (95% CL 1.67 to 3.57 mg/kg), whereas for convulsions induced by strychnine it was higher at 4.25 mg/kg (95% CL 2.32 to 3.78 mg/kg). At the same time, both anticonvulsive doses are significantly lower then the observed LD50 of ivermectin (18.20 mg/kg). Furthermore, flumazenil (0.1 and 0.2 mg/kg), an antagonist of benzodiazepine receptors, antagonizes just one part of these anticonvulsive effects of ivermectin. Our results show the significant anticonvulsive properties of ivermectin and support the findings that ivermectin in the CNS of mammals produces multiple inhibitory effects, probably through participation in the function of GABA-sensitive and GABA-insensitive chloride channels.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, Bulevar JA 18, Belgrade 11000, Serbia and Montenegro. sasa@vet.bg.ac.yu
authors.forename: S M
authors.initials: SM
authors.lastname: Trailović
authors.forename: V M
authors.initials: VM
authors.lastname: Varagić
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D003292:Convulsants / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D007559:Ivermectin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007928:Lethal Dose 50; D008012:Lidocaine / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013331:Strychnine / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000779:Anesthetics, Local; D000927:Anticonvulsants; D000977:Antiparasitic Agents; D003292:Convulsants; D018757:GABA Modulators; D018009:Receptors, Glycine; D005442:Flumazenil; D007559:Ivermectin; D008012:Lidocaine; D013331:Strychnine