Structure-Activity Relationships of Agents Modifying Cholinergic Transmissions
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 1/500th 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1983
- Accession Number
- ADB101201
Entities
People
- J. G. Cannon
- J. P. Long
Organizations
- University of Iowa