Abstract found on PubMed
There are only a few drugs that can seriously lay claim to the title of “wonder drug” and ivermectin, the world’s first endectocide and forerunner of a completely new class of antiparasitic agents, is among them. Ivermectin, a mixture of two macrolytic lactone derivatives (avermectin B1a and B1b in a ratio of 80:20), exerts its highly potent antiparasitic effect by activating the glutamate-gated chloride channel that is absent in vertebrate species. However, in mammals, ivermectin activates several other Cys-loop receptors, including the inhibitory GABAA and glycine receptors and the excitatory nicotinic acetylcholine receptor of brain neurons. Based on these effects on vertebrate receptors, ivermectin has recently been proposed to constitute a multifaceted wonder drug for various novel neurological indications, including alcohol use disorders, motor neuron diseases, and epilepsy. This review critically discusses the preclinical and clinical evidence of anti-seizure effects of ivermectin and provides several arguments why ivermectin is not a suitable candidate drug for the treatment of epilepsy. First, ivermectin penetrates the mammalian brain poorly, so it does not exert any pharmacological effects via mammalian ligand-gated ion channels in the brain unless it is used in high, potentially toxic doses or the blood-brain barrier is functionally impaired. Second, ivermectin is not selective but activates numerous inhibitory and excitatory receptors. Third, the preclinical evidence for anti-seizure effects of ivermectin is equivocal and, at least in part, ED50 s in seizure models are in the range of the LD50 . Fourth, the only robust clinical evidence of anti-seizure effects stems from the treatment of patients with onchocerciasis in which the reduction of seizures is due to a reduction in microfilariae densities but not a direct anti-seizure effect of ivermectin. We hope that this critical analysis of available data will avert that the unjustified hype associated with the recent use of ivermectin to control COVID-19 recurs also in neurological diseases such as epilepsy.