Effects of Aldrin-transdiol on neuromuscular facilitation and depression

Abstract

Effects of aldrin-transdiol on neuromuscular facilitation and depression, European J. Pharmacol. 31 (1975) 166--175.The effects of aldrin-transdiol, one of the active metabolites of the insecticide dieldrin, on evoked transmitter release, neuromuscular facilitation and neuromuscular depression have been studied in frog sartorius nerve--muscle preparations. Conventional techniques of intracellular recordings were used. Aldrin-transdiol caused a marked increase in end-plate potential amplitude under conditions of low quantal content, i.e., in Mg2+-blocked junctions. The increase in end-plate potential amplitude was less pronounced in curarized junctions, in which the transmitter release was not impaired. Concomitant with the increase in end-plate potential size there was a marked enhancement of facilitation during short trains of stimuli applied to the motor nerve. The decay of facilitation was, however, not seriously affected by aldrin-transdiol. These effects may be explained in terms of the known 'calcium hypothesis' by assuming that aldrin-transdiol increases the amount of calcium which enters the nerve terminal during the nerve impulse.The increase in end-plate potential amplitude and in facilitation by aldrin-transdiol was transient. At later stages of poisoning, end-plate potential and facilitation decreased below control level and neuromuscular depression was significantly enhanced. This latter effect may be the result of a direct inhibitory effect of aldrin-transdiol on transmitter mobilization. As far as the fall in end-plate potential amplitude is concerned the known suppressive action of aldrin-transdiol on the chemical sensitivity of the postsynaptic membrane and on the nerve action potential probably plays a part as well. Finally, neuromuscular transmission was completely blocked by aldrintransdiol.

Effects of dieldrin (HEOD) and some of its metabolites on synaptic transmission in the frog motor end-plate

“…A preliminary report of some of this material has appeared (20 and 9-syn-hydroxy-HEOD (9HH) (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-9-hydroxy-endo-1,4-ezo-5,8-dimcthanonaphtalene) were dissolved in 96yo ethanol to make up stock solutions. This was squirted forcefully through a No.…”

Interactions with the Gamma-Aminobutyric Acid A-Receptor

“…However, t-DDA caused prostration only slowly when injected into cockroaches, quite different from the rapid action of dieldrin in vivo. The bioactivation hypothesis was further supported by the neuroactivity of t-DDA observed on frog nerve-muscle preparations (Akkermans et al, 1974(Akkermans et al, , 1975a. The findings for cockroach were confirmed (Schroeder et al, 1977;Shankland and Schroeder, 1973), but, based on the less intense neuroactive effect of the diols and their very slow action in vivo, the diols were concluded to be detoxification products in the cockroach.…”