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.