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The effects of physostigmine on the electroretinogram in the beagle dog

  • Pharmacology
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Abstract

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.

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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

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Authors and Affiliations

  1. Toxicology Department, Miles Inc., 17745 S. Metcalf Avenue, 66085-9104, Stilwell, KS, USA

    R. D. Jones, B. F. Hamilton & P. D. Dass

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  1. R. D. Jones
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  2. B. F. Hamilton
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  3. P. D. Dass
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Jones, R.D., Hamilton, B.F. & Dass, P.D. The effects of physostigmine on the electroretinogram in the beagle dog. Vet Res Commun 19, 135–147 (1995). https://doi.org/10.1007/BF01839280

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