Contribution of Ion Channel-Blocking by Oximes to Their Therapeutic Action Against Soman Poisoning in Vitro
Abstract
Oximes, which reactivate inhibited acetylcholinesterase (AChE), are used to treat poisoning by organophosphorus anticholinesterases. Some oximes produce neuromuscular recovery even when the inhibited AChE has undergone dealkylation ('aging') and can no longer be reactivated. It has been proposed that at least part of this direct recovery may be due to blockade of nicotinic ion channels. I have tested this hypothesis by comparing the direct recovery produced by a range of these compounds with their channel-blocking activities. Direct recovery was measured in soman-poisoned diaphragms from guinea pigs. Single channel recordings were made from the endplates of dissociated adult mouse flexor digitorum brevis muscle fibres. Both oximes and non-oxime analogues could produce direct recovery. The compounds which caused the greatest recovery also produced a very rapid, flickering type of open channel blockade. several parameters of channel blockade showed strong correlations with the degree of recovery measured in diaphragms over the range of 12 compounds tested.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008833
Entities
People
- John E. Tattersall