Drug blockade of open end‐plate channels.

Abstract

4. Conductance changes produced by bath applied agonists were depressed by thiopentone, the effect becoming greater the higher the agonist concentration. This effect, and also the observation that the concentration of thiopentone required to depress the bath agonist response is much greater than the apparent dissociation constant for binding to active receptor-channel complexes calculated from kinetic measurements, suggest that the selectivity for binding to open receptor-channel complexes is very high.5. Methyprylone, which is structurally similar to the barbiturates, is only a weak antagonist and shows no interpulse interaction. It was predicted that methyprylone should produce fast and slow components in the e.p.c. decay, and this prediction was verified.6. In the presence of barbiturates large iontophoretic carbachol applications produce conductance changes which show fast and slow components. Under these conditions the effects of carbachol prepulses become complex. However the effects are qualitatively consistent with the notion that different components of the response are contributed by channels located at various distances from the iontophoretic pipette tip.

Actions of pentobarbital on rat brain receptors expressed in Xenopus oocytes

“…The reason for this is not clear. Possibilities include a plugging of the chloride channels by high concentrations of barbiturate, similar to that seen at ACh-activated endplate channels (Adams, 1976); occupation of the GABA receptor sites; or reversal of the enhancement of GABA binding (Willow and Johnston, 1980). Whatever its origin, the depression at high barbiturate concentrations was rapidly reversible, since the responses often increased transiently, before falling, when GABA and barbiturates were washed from the oocyte.…”

Postsynaptic Effects of Some Central Stimulants at the Neuromuscular Junction

“…This is illustrated in Figure 9. (Adams, 1974;1976). Such a mechanism might also account for the effects reported here.…”

“…Results 5-Ethyl-5-(3 '-methyl-but-2 '-enyl) barbituric acid (3M2B) Many anaesthetic barbiturates have been shown to reduce the time constant of decay of endplate currents (Adams, 1974;1976;Seyama & Narahashi, 1975;Torda & Gage, 1976). There have been re-ports that 5-ethyl-5-(3'-methyl-but-2'-enyl) barbituric acid (3M2B), an analogue of amylobarbitone, causes convulsions in whole animals (Taylor & Noble, 1949;Andrews, Jones & Lodge, 1979 Figure 2b.…”

Nicotinic Acetylcholine Receptors

“…Competitive block was already formulated quantitatively in 1937 (Gaddum, 1937). In contrast with channel blocking agents, which were discovered only in the 1970s (Blackman, 1970;Armstrong & Hille, 1972;Adams, 1976). It was soon discovered how to make robust estimates of the equilibrium constants for competitive antagonists from measurements of responses (Schild, 1947;Arunlakshana & Schild, 1959), and soon after by direct measurement of ligand binding (Paton & Rang, 1965).…”