Protection by Tacrine and Some Adjuncts against the Depressant Effects of Soman in Guinea-Pig Atrium
Abstract
The negative inotropic effects of soman have been reported previously. It was suggested that the depression in atrial force of contraction was a consequence of continuous muscarinic receptor activation by excessive acetylcholine (ACh) accumulation and also possibly through direct interactions at the receptor-associated K+ channels by organophosphate (OP). In this study, the protective effects of tacrine (THA), an antimuscarinic as well as a K+ channel blocker, against soman in guinea-pig atrium were investigated. It was found that tacrine could antagonize the negative inotropic effects of soman. This antagonism occurred in a concentration dependent manner, with effective concentrations (ECs) fore tacrine ranging from 1.7 to 12.1 micrometers when the atrium was equilibrated with 0.05-10 micrometers soman. Inclusion of an oxime HI-6 (100 micrometers) in the regimen improved the efficacy of tacrine against soman (1 micrometer) by 16.1 fold. Addition of a potent antimuscarinic, either atropine or glycopyrrolate with tacrine also improved tacrine's efficacy against soman significantly. Atropine, at equivalent concentration, appeared to be the most effective of the three. At 0.1 micrometers concentration, atropine was 4.25 and 3.47 times more potent than HI-6 and glycopyrrolate respectively in enhancing THA efficacy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1993
- Accession Number
- ADA283795
Entities
People
- Wai-man Lau
Organizations
- Defence Science and Technology Group