Accession Number:

ADA171512

Title:

Effects of Chemical Agents on the Cholinergic Neurotransmitter System: Mechanisms of Adaptation.

Descriptive Note:

Annual rept. 18 Apr 83-17 Apr 84,

Corporate Author:

CALIFORNIA UNIV LOS ANGELES

Personal Author(s):

Report Date:

1984-06-20

Pagination or Media Count:

118.0

Abstract:

The research was designed to investigate behavioral and neurochemical adaptation during acute and chronic exposure to chemicals affecting the cholinergic neurotransmitter system. Two newly-synthesized mustard analogs of oxotremorine were found to have similar pharmacological properties as agonists binding specifically to muscarinic receptors mAChRs. Chronic administration of these compounds reduced receptor binding to less than 10 of normal and produced dramatic differences in recovery rates following withdrawal heart recovered most rapidly, then muscle, with brain slowest. Acute effects on behavioral and physiological functions were followed by sustained resistance to cholinergic agonists, the protection involving central nervous system mechanics. Comparisons of effects of these irreversible compounds with those of the reversible agonist, oxotremorine, confirmed the observations that the former produce a sustained change in receptor-mediated events which would be expected from an irreversible ligand. The results also suggest widely differing sensitivities of different neural circuits to interference by the irreversible agonists. These differences have significant implications for effects of direct cholinergic agonists and compounds, e.g. anticholinesterase, which act as indirect agonists by increasing acetylcholine levels in brain and other tissues.

Subject Categories:

  • Toxicology
  • Pharmacology
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE