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.
Jones
R D
RD
Toxicology Department, Miles Inc., Stilwell, KS 66085-9104, USA.
Hamilton
B F
BF
Dass
P D
PD
D000818:Animals; D002802:Cholinesterases / Q000187:drug effects / Q000378:metabolism; D003315:Cornea / Q000201:enzymology; D004285:Dogs / Q000502:physiology*; D004596:Electroretinography / Q000187:drug effects / Q000662:veterinary; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D007262:Infusions, Intravenous / Q000662:veterinary; D008297:Male; D009801:Oculomotor Muscles / Q000201:enzymology; D010830:Physostigmine / Q000008:administration & dosage / Q000633:toxicity*; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*
D010830:Physostigmine; D002802:Cholinesterases