Effects of Central Depressant Drugs Upon Acetylcholine Release

Abstract

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.

Centrally Active Drugs and Transmission Through the Isolated Superior Cervical Ganglion Preparation of the Rabbit When Stimulated Repetitively

“…These compounds shared none of the three properties of the Group A drugs and therefore repetitive stimulation would be expected to have no effect on the degree of block. Methylpentynol carbamate appears in Group C and it is interesting to note that Marley & Paton (1959) have reported that it has a ganglion-stimulant action in the perfused ganglion of the cat, a finding confirmed by Matthews & Quilliam (1964). The reversal by repetitive stimulation of the block of transmission of single impulses produced by adrenaline (Fig.…”

The action of pentobarbitone on stimulus‐secretion coupling in adrenal chromaffin cells

“…This effect occurred at concentrations of pentobarbitone comparable to those required for the maintenance of general anaesthesia. Later Matthews & Quilliam (1964) showed that the closely related barbiturate, amylobarbitone, depressed the release of acetylcholine in response to nerve stimulation. Barbiturates also depress the sensitivity of sympathetic ganglion cells to exogenously applied nicotinic agonists (Nicoll & Iwamoto, 1976).…”

The Effect of Amethocaine on Acetylcholine‐induced Depolarization and Catecholamine Secretion in the Adrenal Chromaffin Cell

“…Local anaesthetics are known to depress acetylcholine output from cholinergic nerves in relatively low concentrations (Harvey, 1939;Furukawa, 1957;Straughan, 1961 ;Matthews & Quilliam, 1964;Paton & Thomson, 1964) and also inhibit the output of vasopressin from neurohypophyses stimulated electrically (Haller, Sachs, Sperelakis & Share, 1965). The only explanation that has been offered for these effects is that the local anaesthetics may block impulse propagation in the terminals.…”