Substances blocking sympathetic post‐ganglionic fibres and the neuromuscular junction.

Abstract

In an earlier paper Burn & Froede (1963) described the action exerted on post-ganglionic sympathetic fibres by phenyltrimethylammonium. They showed that this substance, like bretylium, blocked the response to stimulation according to the frequency used, and that stimulation at high frequencies was blocked earlier than stimulation at low frequencies. This indicated that the action was not that of a local anaesthetic. They chose phenyltrimethylammonium because Riker (1953) had shown that it had a curare-like action at the neuromuscular junction, and it was therefore well suited to test the view that substances which blocked the action of acetylcholine at the neuromuscular junction would also block the release of noradrenaline by impulses passing along the sympathetic post-ganglionic fibres. This view was based on the hypothesis of Burn & Rand (1959) that the sympathetic impulse first released acetylcholine, and this in turn released noradrenaline.Dixit, Gulati & Gokhale (1961) showed that both bretylium and guanethidine blocked the response of the rat diaphragm to stimulation of the phrenic nerve without affecting the response to direct stimulation of the diaphragm. They compared these substances with decamethonium and D-tubocurarine. The significance of their results has been criticized on the ground that the concentrations of bretylium and of guanethidine needed to block the phrenic nerve-diaphragm preparation were high, and that a feeble action was of no significance. We have therefore repeated the observations of Dixit et al. on bretylium and guanethidine, and we have also examined the action of mecamylamine on the phrenic nerve-diaphragm. Recently Burn & Gibbons (1964a) showed that mecamylamine exerted a blocking action in the sympathetic post-ganglionic fibre. We have also tested the action of D-tubocurarine, dihydro-,8-erythroidine, tetraethylammonium and decamethonium on the sympathetic postganglionic fibre.

The Effect of Calcium in Removing the Blocking Action of Bretylium and Guanethidine

“…Other substances which block the response to the sympathetic impulse include d-tubocurarine and dihydro-/?-erythroidine (Burn & Seltzer, 1965) and also mecamylamine and pempidine (Burn & Gibbons, 1964b). Thus it is evident that the response to the sympathetic impulse is blocked by agents which block the action of acetylcholine at the neuromuscular junction and at the sympathetic ganglion.…”

Blockade of Adrenergic and Cholinergic Transmissions by Emetine

“…Since mecamylamine, which is also a secondary amine, has been found to act like bretylium at the sympathetic post-ganglionic terminations (Burn & Gibbons, 1964) and since mecamylamine resembles bretylium in causing block of the neuromuscular junction in skeletal muscle (Burn & Seltzer, 1965) it seemed possible that emetine might act like bretylium. In a preliminary study, Ng (1966a) showed that emetine abolished both the motor and inhibitory responses of the effector organs to stimulation of the sympathetic post-ganglionic fibres.…”

Some Relationships Between Chemical Structure and Pharmacological Activities

“…Bebbington & Brimblecombe (38) conclude that among oxotremorine ana Agents as varied as tubocurarine, TEA, decamethonium, guanethidine, and pempidine, which block ACh at the neuromuscular junction or at sympa thetic ganglia, also appear capable of blocking release of norepinephrine from sympathetic post-ganglionic fibers (58).…”