Accession Number:

ADA202893

Title:

Pathophysiology of Anticholinesterase Agents

Descriptive Note:

Annual rept. 15 Mar 1986-14 Mar 1987

Corporate Author:

COLORADO STATE UNIV FORT COLLINS DEPT OF ANATOMY

Personal Author(s):

Report Date:

1987-09-21

Pagination or Media Count:

163.0

Abstract:

We complete the description of the acute, delayed, and long-term effects on rat neuromuscular junction NMJ ultrastructure and physiology following single acute injections of very low to near lethal doses of physostigmine, a reversible anticholinesterase anti-ChE compound. We also complete the descriptions of the immediate and long term effects of subacute exposures at doses which produce sustained blood ChE inhibitions of 40 or - 10 and 80 or - 10 for up to 14 days and of the reversibility of effects during recovery for 3-28 days following termination of subacute exposure. In additional correlative experiments using guinea pigs as alternative models to rats, sub-lethal but acute high doses of physostigmine produced equally severe and apparently identical pathological alterations in endplate ultrastructure at similar blood ChE inhibition levels. We conclude that the rat and guinea pig are essentially equivalent as models for characterizing the ultrastructural alterations of neuromusuclar junctions caused by acute high doses of physostigimine. Finally, we present additional physiological and ultrastructural data showing that the threshold for producing neuromuscular pathology is lowered i.e., toxic alterations of the endplates are increased by sustained neuromuscular activity. These data may be of value in evaluating and comparing anti-ChE medications and dosages used for protection against the irreversible anti-ChE agents. AW

Subject Categories:

  • Toxicology
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE