The effects of physostigmine on the electroretinogram in the beagle dog

The purpose of the study was to correlate electroretinogram (ERG) parameters with increasing levels of plasma, erythrocyte and ocular tissue cholinesterase inhibition using the beagle dog as a model for human neurovisual toxicity. The anticholinesterase compound physostigmine was administered at various steady-state intravenous infusion rates based on pharmacokinetic estimates of plasma and red blood cell cholinesterase inhibition. The most sensitive parameter was the b-wave amplitude of the rod response, which was significantly depressed compared to pretreatment at all levels of acute cholinesterase depression. The overall maximal ERG response demonstrated a trend of declining a-and b-wave amplitudes, which corresponded with the increased levels of cholinesterase depression, but these differences were not significant. The depression of the electroretinogram rod and cone amplitudes appeared to parallel plasma cholinesterase inhibition more closely than erythrocyte cholinesterase activity. Ocular tissue cholinesterase activity was significantly depressed in the retina (70%), cornea (60%) and dorsal rectus extraocular muscle (46%). Electroretinography may be a useful physiological tool for evaluating the ocular toxicity of certain chemicals or pharmaceuticals associated with cholinesterase biomarker activity.Abbreviations AChE acetylcholinesterase - Amp amplitude - BuChE butyrylcholinesterase - C _p plasma level - C _ss steady-state plasma concentration - D _L loading dose - e ^–kt the rate of elimination over time (t) - ERG electroretinogram - k elimination rate constant - Lat latency - MBW metabolic body weight - O₁–O₅ consecutive oscillatory potential wavelets - PreTx pretreatment - R rate of infusion - R _Inf rate of infusion - V _d volume of distribution