This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
The higher parts of the nervous system have the power of lessening the action of the lower, and in the frog this power seems to be especially marked in the optic lobes. Irritation of these either mechanically by a needle, chemically by a grain of salt laid upon them, or electrically, will lessen or entirely abolish the reflex action in the cord; but this again returns when the irritation is removed, or when its influence is destroyed by cutting the cord across, below the point of irritation. This fact was discovered by Setschenow, and thus parts of the optic lobes concerned in this inhibitory action are known as Setschenow's centres.
1 Schmiedeberg, Arzneimitlellehre, p. 34.
An inhibitory action appears to be exerted by the cranial centres in higher animals also, for McKendrick observed that on decapitating a pigeon the body lies comparatively still for a second or two, and then violent convulsions set in. If the body be held firmly during these convulsions, and a moderately strong faradaic current be applied to the upper part of the spinal cord, the convulsions may be altogether arrested while it continues, again commencing when it stops. In this experiment the application of the current to the cut end of the cord is regarded as supplying a stimulus in place of that which would normally pass downwards from the brain.
Quinine causes great depression of reflex excitability, and this was stated by Chaperon to be due to the action of the drug on Setschenow's centres.
Fig. 60. -Nervous system of a frog, showing the cerebral and optic lobes, the medulla oblongata, and the spinal cord with nerve-roots. The brain is shown on a larger scale at p. 184.
Almost immediately after injection of quinine into the dorsal lymph-sac, the reflex excitability of the frog becomes very greatly reduced or almost entirely abolished, but if the spinal cord be now cut across at its upper part just below the medulla oblongata, the reflex excitability becomes as great, or even greater, than the normal.
This loss of excitability has been ascribed by Binz to the action of quinine on the heart, causing weakening of the circulation, and thus indirectly producing paralysis of the cord. This kind of paralysis does occur with large doses and after considerable time, but it is quite different from the inhibitory paralysis described by Chaperon, which comes on almost immediately after the injection of the drug into the lymph-sac, and disappears immediately on section of the cord below the medulla.
I have repeated Chaperon's experiments, and can fully confirm their accuracy. In doing so, however, it struck me that the result was most marked when a solution of quinine was concentrated and somewhat strongly acid. It therefore appeared probable that the inhibition was not due to the direct action of the quinine upon Setschenow's centres after it had been carried to them by the blood, but only to its reflex action upon them. It irritates locally the sensory nerves of the lymph-sac into which it is injected, and this stimulus being transmitted to the optic lobes excites them so that they produce inhibition of that reflex action which would usually occur in the cord when the foot is irritated by acid. On testing this hypothesis by injecting acid alone into the lymph-sac, Mr. Pardington and I found that it also caused reflex inhibition like that produced by quinine. We may therefore conclude that there is nothing special in the action of quinine upon the inhibitory centres; it merely acts like other irritants on sensory nerves.1 Probably digitalis and sanguinaria also act in a similar way.