Abstract:
The inhibitory glycine receptor, a ligand-gated ion channel that mediates fast synaptic inhibition in mammalian spinal cord and
brainstem, is potently and selectively inhibited by the alkaloid strychnine. The anthelminthic and anticonvulsant ivermectin is a
strychnine-independent agonist of spinal glycine receptors. Here we show that ivermectin is an effective antidote of strychnine
toxicity in vivo and determine time course and extent of ivermectin protection. Mice received doses of 1 mg/kg and 5 mg/kg
ivermectin orally or intraperitoneally, followed by an intraperitoneal strychnine challenge (2 mg/kg). Ivermectin, through both
routes of application, protected mice against strychnine toxicity. Maximum protection was observed 14 hours after ivermectin
administration. Combining intraperitoneal and oral dosage of ivermectin further improved protection, resulting in survival rates of
up to 80% of animals and a significant delay of strychnine effects in up to 100% of tested animals. Strychnine action developed within
minutes, much faster than ivermectin, which acted on a time scale of hours. The data agree with a two-compartment distribution
of ivermectin, with fat deposits acting as storage compartment. The data demonstrate that toxic effects of strychnine in mice can
be prevented if a basal level of glycinergic signalling is maintained through receptor activation by ivermectin.
