Further studies on node of Ranvier inactivation by electronegatively substituted tropanyl esters

Abstract

In further study of the actions of monosubstituted phenylacetate esters of tropine and ψ-tropine on excitability of nodes of Ranvier in frog sciatic nerve fibers, the effects of m-NO 2 and m-F substitution have now been determined. These electronegatively substituted esters are quite active in the incubating concentration range 3.0–7.5 m m, depressing the peak nodal action current level moderately and raising the threshold stimulation voltage markedly. Ester strength in blockade of nodal excitability appears to be relatively independent of the stereochemical mode of attachment in the 3-tropanyl ring system, but the degree of reversibility of effects on washing does vary with this structural parameter. From the series of potency indexes for these esters, it appears that antinodal activity decreases regularly with increasing electronegativity of the aryl group substituent. This relationship has been applied in probing possible structures of nodal receptors inactivated by the tropanyl esters.