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.
Fig. 66. - Diagram illustrating Magendie's method of investigating the mode of action of upas (strychnine). A, femoral vein; B, peritoneum; c, pleura; d, femoral artery; E, F, g, spinal cord, to which small arteries are seen passing from the aorta. At F is indicated a point of section of the cord.
The next question was whether the convulsions were caused by the action of the drug on the brain or the cord.
To ascertain its action upon the brain, a little of the solution was injected into the carotid artery. The effects produced were the same as those of any irritating liquid. The intellectual faculties disappeared, the head was laid between the paws, and the animal rolled over and over like a ball. These effects passed off as the circulating blood removed a quantity of the drug from the brain, and were succeeded by the ordinary tetanic convulsions when sufficient time had elapsed for it to reach the spinal cord. The question whether it really acted upon the cord still remained to be put to a crucial test. If its effects were really due to its action upon the spinal cord they ought to cease upon the destruction of that part of the nervous system, and to occur when the drug was applied to it alone. The cord was therefore destroyed by running a piece of whalebone down the vertebral canal at the moment of injection. When this was done, no tetanus occurred. In another experiment, Magendie waited until the tetanic spasms had been induced by the upas, and then destroyed the spinal cord by slowly pushing the whalebone down the vertebral canal. As the whalebone advanced, the tetanus disappeared, first in the fore-legs, when the dorsal part of the cord was destroyed, and then in the hind-legs, when the whalebone had reached the lumbar vertebrae.
In another experiment, an animal was narcotised by means of opium, and the spinal canal laid freely open. The upas was then directly placed on a part of the spinal cord. Tetanus immediately occurred in that part of the body, and in that part only to which the nerves arising from this portion of the cord were distributed. When the poison was successively applied to other parts of the cord, the convulsions spread to the corresponding regions of the body.
The question whether a drug exercises a convulsant action through the brain or spinal cord is now frequently tested, not by destroying the whole cord as Magendie did, but simply by dividing the spinal cord transversely between the occiput and the atlas. Convulsions depending upon stimulation of the motor centres in the brain and medulla oblongata then cease after section, while those dependent upon the spinal cord do not.
The experiment of dividing the spinal cord transversely about its middle is also sometimes performed in order to test whether the convulsions are of really spinal origin. If they are, they should persist in both the anterior and posterior parts of the body, but if they are of cerebral origin, they occur in the anterior but not in the posterior part.
The effect of strychnine and allied substances upon the cord is usually ascribed to increased excitability of the nerve-cells, but it is not improbably due partly to alteration in the comparative rate at which stimuli are transmitted from one cell to another; but this subject has already been more fully discussed under ' Inhibition ' (q.v., p. 173 et seq.).
Some curious results obtained by Dr. A. J. Spence may be explained on the latter hypothesis which would be inexplicable on the former. After removing the blood from the body of a frog, and exposing the brain, he placed some nux vomica upon it, so that it could gradually diffuse along the spinal cord. As it passed downwards he observed that, at first, irritation of the fore-feet caused spasm only in them; later it caused spasm of both front and hind-feet, while irritation of the hind-feet still produced the ordinary reflex; and later still irritation of the fore-feet caused no spasm in the hind-legs while irritation of the hind-feet would still cause spasm in the fore-legs.1
The action of strychnine on the conducting power of the spinal cord has already been discussed. It diminishes or abolishes the power of summation, but increases the reflex excitability, so that stimuli will produce reflex action which are too feeble to do so when the spinal cord is in its normal condition. The difference between the reaction to strong and weak stimuli is also to a great extent abolished, and both produce tetanic contractions. This condition, however, is absent for a short time after the application of each stimulus, and then strong and weak stimuli produce corresponding strong and weak action, much as in the normal cord.2
The effect of nicotine as a spinal stimulant is very extraordinary; for Freusberg found that when frogs had been decapitated for twenty-four hours, and reflex action was almost entirely gone, the injection of a small quantity of the poison increased the reflex excitability so much that irritation of the skin caused well-marked movements. This increase lasted from one to three days, and the bodies of frogs poisoned by nicotine retained a fresh appearance for a long time.