The Mechanism of Action of Paraldehyde and Methylpentynol on Neuromuscular Transmission in the Frog

Self Cite

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.

mentioning

confidence: 99%

Effects of Central Depressant Drugs Upon Acetylcholine Release

Matthews

Quilliam

1964

Self Cite

“…The preganglionic blocking activity of amylobarbitone accords with the findings of Exley (1954) and those of Matthews & Quilliam (1964) that this drug can cause some decreased output of acetylcholine from the cat perfused ganglion. The latter authors also found by direct measure-ment that paraldehyde could reduce acetylcholine output, an action which had been postulated for the drug by Nicholls & Quilliam (1956) at the skeletal neuromuscular junction and by Quilliam (1959) at the ganglionic synapse.…”

Section: Potencies Of Ganglion-blocking Drugsmentioning

confidence: 83%

The Selectivity of Drugs Blocking Ganglionic Transmission in the Rat

Quilliam¹,

Shand²

1964

Self Cite

By comparing the effects on ganglionic transmission and on the pre-and postganglionic 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.Many drugs of varied chemical structure can block ganglionic transmission. The present investigation was carried out in an attempt to estimate quantitatively the action of some of these drugs upon the component parts of a typical peripheral ganglionic synapse by comparing their effects on ganglionic transmission and on conduction in the pre-and postganglionic nerves of the isolated superior cervical ganglion preparation of the rat. METHODSWistar strain rats of either sex, weighing between 150 and 250 g, were anaesthetized with 1.5 g/kg of urethane injected intraperitoneally, which does not block ganglionic transmission in anaesthetic doses (Larrabee & Posternak, 1952). The superior cervical ganglion with its postganglionic internal carotid nerve and the preganglionic cervical sympathetic trunk was then excised, transferred to a dish of Krebs solution at room temperature and bubbled with a mixture of 95% oxygen and 5% carbon dioxide, and the connective tissue sheath around the ganglion and the postganglionic nerves was removed.The preparation was then mounted horizontally in a bath of Krebs solution at 30' C equilibrated with 95% oxygen and 5% carbon dioxide. Stimuli, in form of rectangular pulses of 500 ,usec duration and of variable voltage, could be applied through a pair of platinum stimulating electrodes (Fig. 1, S) linked by an isolating transformer to a stimulator like that described by Bell (1957). Stimuli were delivered at 6 shocks/min, a frequency at which successive stimuli showed minimal interaction. The nonpolarizable silver-silver chloride-agar saline recording electrodes (Fig. 1, R1 to R5) with balsa wood tips or bristle wicks were connected to a DC amplifier (Copeland, 1952), a calibrator and a cathode-ray oscilloscope. For recording, the preparation was raised above the fluid level in the bath, so providing moist

“…The decrease in acetylcholine output produced by these agents was generally less marked than that with procainamide or procaine and was not readily correlated with the degree to which transmission through the ganglion was blocked. Methylpentynol and paraldehyde also impair the release of acetylcholine from motor nerves (Nicholls & Quilliam, 1956;Matthews & Quilliam, 1964).…”

Section: Discussionmentioning

confidence: 99%

Observations on the Mode of Action of Some Central Depressant Drugs on Transmission Through the Cat Superior Cervical Ganglion

Brown

Quilliam

1964

Self Cite

Methylpentynol, paraldehyde, amylobarbitone and procainamide blocked transmission through the cat superior cervical ganglion, and antagonized the ganglionstimulating 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 antiacetylcholine 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.