The effect of some centrally-active and other drugs on the transmission of single nerve impulses through the isolated superior cervical ganglion preparation of the rabbit has been studied by recording both preganglionic and postganglionic action potentials. Block of conduction in the axon could be distinguished from block of the synaptic mechanism. The drugs did not appear to exert any one characteristic form of blocking action. A continuous spectrum of drug action linked an agent such as meprobamate which acted predominantly on the synapse to benactyzine which acted mainly by blocking axonal conduction. The drugs have been divided into three groups. Group I: hexamethonium, meprobamate, paraldehyde, amylobarbitone, methylpentynol and azacyclonal; these acted relatively selectively at the ganglion. Group II: N714C (the cis-isomer of chlorprothixene), prochlorperazine, methylpentynol carbamate, pipradrol, promethazine, perphenazine and procaine; the action of these drugs on the ganglion could be accounted for entirely in terms of their axonal depressant action. Group III: chlorprothixene, promazine, N720 (dihydrochlorprothixene), chlorpromazine, hydroxyzine and benactyzine; these drugs also blocked axonal conduction but in addition they appeared to exert a "facilitating" action at the ganglionic synapse. The actions of adrenaline, adrenochrome, iproniazid, ergotoxine, mescaline and lysergic acid diethylamide on transmission were also studied. The implications of the modifications of ganglionic transmission produced by these drugs is discussed.

Action Potentials↗

PubMed1964

OBSERVATIONS ON THE MODE OF ACTION OF SOME CENTRAL DEPRESSANT DRUGS ON TRANSMISSION THROUGH THE CAT SUPERIOR CERVICAL GANGLION.

Methylpentynol, paraldehyde, amylobarbitone and procainamide blocked transmission through the cat superior cervical ganglion, and antagonized the ganglion-stimulating actions of acetylcholine and carbachol injected intra-arterially to the ganglion. Comparison with the effects of tetraethylammonium indicated that the impaired response to acetylcholine could not wholly account for the failure of transmission, which suggested that an impaired release of transmitter substance was a contributory factor. Methylpentynol, paraldehyde and procainamide also blocked the ganglion-stimulating action of potassium chloride. In contrast, amylobarbitone and pentobarbitone did not block the stimulating action of potassium chloride, but antagonized specifically the actions of acetylcholine and carbachol. The anti-acetylcholine activities of the two barbiturate drugs at this site accord with their relative ganglion-blocking activities. It is concluded that the ganglion-blocking action of methylpentynol, paraldehyde and procainamide arises from a nonspecific depression of both presynaptic and postsynaptic elements in the ganglion, but that barbiturate compounds act more specifically on the acetylcholine receptor.

Acetylcholine↗

PubMed1964

THE SELECTIVITY OF DRUGS BLOCKING GANGLIONIC TRANSMISSION IN THE RAT.

By comparing the effects on ganglionic transmission and on the pre- and post-ganglionic nerves in the isolated superior cervical ganglion preparation of the rat, the selectivity of several drugs was assessed quantitatively. Hexamethonium, tetraethylammonium, nicotine and tubocurarine blocked transmission in concentrations which did not affect nervous conduction and were considered to be highly selective in action. Atropine, amylobarbitone and paraldehyde depressed nervous conduction appreciably in ganglion-blocking doses, but not enough to account wholly for the block in transmission and they were therefore considered as being moderately selective. The ganglion blocking actions of mephenesin, procaine, methylpentynol, methylpentynol carbamate and benactyzine were nonspecific, showing general depression of neuronal activity. Ganglion block with bretylium was nonselective in its site of depression of the postganglionic neurone in concentrations which only partly depressed the preganglionic nerve.

Atropine↗

PubMed1964

EFFECTS OF CENTRAL DEPRESSANT DRUGS UPON ACETYLCHOLINE RELEASE.

Several central depressant and other drugs have been examined for their effects upon acetylcholine release from the stimulated, perfused cat superior cervical ganglion and rat isolated phrenic nerve-diaphragm preparations. The acetylcholine released was assayed biologically. Amylobarbitone sodium, chloral hydrate, trichloroethanol, methylpentynol, methylpentynol carbamate, paraldehyde, procaine hydrochloride and troxidone reduced the presynaptic release of acetylcholine from the ganglion. They also exhibited a postsynaptic blocking action, this component of depressant activity being particularly prominent with paraldehyde and troxidone. Closely analogous findings were obtained at the neuromuscular junction with methylpentynol and its carbamate, paraldehyde, procaine hydrochloride, trichloroethanol and troxidone. At both sites the drug-induced depression, both of transmission and of acetylcholine output, was reversible. Whereas hexamethonium regularly blocked ganglionic transmission with no effect upon acetylcholine release, tetraethylammonium not only completely blocked ganglionic transmission but concomitantly augmented acetylcholine output. These results are discussed in relation to the electrophysiological and metabolic events associated with neuro-effector transmission.

Acetylcholine↗

PubMed1959

Some pharmacological properties of the alpha-toxin of staphylococcus pyogenes.

The alpha-toxin of Staphylococcus pyogenes produced a slowly developing contracture of isolated preparations of rabbit jejunum and of guinea-pig ileum which persisted after thorough washing and left the gut unresponsive to further doses of alpha-toxin or of acetylcholine. After incubation with antitoxin, the alpha-toxin no longer produced a contracture. Antitoxin only prevented the alpha-toxin response if added to the bath fluid before but not after the alpha-toxin. Certain drugs reduced the alpha-toxin contracture when added to the bath fluid before or after the alpha-toxin, but the contracture reappeared on washing. Papaverine abolished the contracture and pethidine was only slightly less active. Mepyramine, amyl nitrite, caffeine, aminophylline, adrenaline and ephedrine partly reduced the contracture. Hexamethonium, cocaine, tubocurarine and gallamine had no effect. The effect of atropine was only small. The gut-stimulant activity/haemolytic unit of two alpha-toxin samples differed greatly; this difference did not appear to be due to activity of impurities. The implications of these observations are discussed.

Acetylcholine↗

PubMed1959

Paraldehyde and methylpentynol and ganglionic transmission.

Paraldehyde and methylpentynol blocked transmission of nerve impulses through the superior cervical ganglion of the cat when the drugs were administered intra-arterially to the ganglion or intravenously using the nictitating membrane as an indicator. Electrical studies showed that concentrations of methylpentynol and paraldehyde which blocked transmission in the isolated rat superior cervical ganglion were without action on the preganglionic nerve fibre. In amounts which blocked transmission in the isolated rat ganglion, paraldehyde had no depolarizing activity directly on the ganglion cells and did not interfere with the depolarizing activity of added acetylcholine. The results suggest that the block in transmission of the impulse could be accounted for by a decrease in the release of acetylcholine from the preganglionic nerve terminals. In both species the block was reversible.

Acetylcholine↗

PubMed1957

The mechanism of action of murexine on neuromuscular transmission in the frog.

Murexine (urocanoylcholine, [2-beta-imidazol-4(5)-ylacryloyloxyethyl]trimethylammonium chloride hydrochloride) produced a contracture like acetylcholine in the frog rectus and a neuromuscular block in the rat diaphragm which was not relieved by neostigmine but was antagonized by hexamethonium. Using the foot muscle of the frog, electrical recordings showed that murexine produced a neuromuscular block and depolarized the end-plate region. These effects were similar to those seen with suxamethonium, decamethonium and acetylcholine. While murexine had the same depolarizing potency as decamethonium, it was only one-tenth as active as suxamethonium and acetylcholine. It was concluded that murexine could be classified as a "depolarizing type" of neuromuscular blocking agent but was less potent than suxamethonium.

Acetylcholine↗

PubMed1956