Accession Number:

ADB101201

Title:

Structure-Activity Relationships of Agents Modifying Cholinergic Transmissions

Descriptive Note:

Annual progress rept. no. 1, 1 Sep 1982-31 Aug 1983

Corporate Author:

IOWA UNIV IOWA CITY

Personal Author(s):

Report Date:

1983-09-01

Pagination or Media Count:

36.0

Abstract:

The purpose of this research is the synthesis and biological evaluation of analogs of hemicholinium HC-3. These are agents which decrease the ability of cholinergic neurones to synthesize acetylcholine. The long-range goal of this research is to develop compounds which can be used to antidote excess acetylcholine within a cholinergic synapse. Some possible approaches are 1 decrease the content of acetylcholine within the cholinergic neurone by interfering with synthesis, 2 desensitizing cholinergic receptors at post- synaptic sites, 3 decreasing the release of acetylcholine from the neurone by stabilizing the membrane or via pre-synaptic receptors which when activated will diminish the amount of acetylcholine released into the synapse. Thus far 3 agents have been prepared and evaluated for activity. Two of the agents, which are quarternary amines, approximate HC-3 in activity and the tertiary amine derivative is approximately 1500th as active as HC-3. The latter agent is the first active non-quarternary amine to be reported. The biological assay procedures have been developed to evaluate these agents. Keywords High performance liquid chromatography Incubation Caudate nucleus Rats Rabbits Nerve-gastrochemisumuscle In viro analysis Neuro-muscular blocking Phrenic nerve-diaphragm muscle In vitro analysis and Neuromuscular transmission.

Subject Categories:

  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE