caa a22 4500 463237196 CHVBK 20180405153301.0 cr unu---uuuuu 170326e20071001xx s 000 0 eng 10.1007/s11259-007-0050-3 doi (NATIONALLICENCE)springer-10.1007/s11259-007-0050-3 The Effect of Ivermectin on Convulsions in Rats Produced by Lidocaine and Strychnine [Elektronische Daten] [S. Trailović, V. Varagić] 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 of ivermectin 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. Springer Science + Business Media, Inc., 2007 ivermectin nationallicence convulsions nationallicence GABA nationallicence glycine nationallicence ED50 : median effective dose nationallicence GABA : γ-aminobutyric acid nationallicence LD50 : median lethal dose nationallicence Trailović S. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, Bulevar JA 18, 11000, Belgrade, Serbia and Montenegro aut Varagić V. School of Medicine, Department of Pharmacology, University of Belgrade, Serbia and Montenegro aut Veterinary Research Communications Springer Netherlands 31/7(2007-10-01), 863-872 0165-7380 31:7<863 2007 31 11259 https://doi.org/10.1007/s11259-007-0050-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11259-007-0050-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Trailović S. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, Bulevar JA 18, 11000, Belgrade, Serbia and Montenegro aut NATIONALLICENCE 700 1- Varagić V. School of Medicine, Department of Pharmacology, University of Belgrade, Serbia and Montenegro aut NATIONALLICENCE 773 0- Veterinary Research Communications Springer Netherlands 31/7(2007-10-01), 863-872 0165-7380 31:7<863 2007 31 11259 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer