Magendie, who made the first study of the actions of strychnine, found that, by previously destroying the spinal cord, no convulsions followed the administration of a poisonous dose. The precise agency of the cord is disputed, but it is in a high degree probable that the condition is one of exaggerated reflex excitability, so that the smallest possible peripheric irritation induces a response in the reflex motor center. When Setschenow's inhibiting center of reflex movements is withdrawn as in the decapitated frog, the spasms are induced as before. The passage over the face of the faintest current of air, even the mental conception of such an impression, will excite the spasms. Absolute repose, as by placing the poisoned frog under a bell-glass, the table firm so that no jar can reach the animal, and light excluded, has a decided effect in preventing attacks. If a poisoned human subject is similarly protected, the convulsions are diminished in violence. Again, if, when the convulsions are impending, the limbs are firmly grasped and held, the force of the spasm is lessened thereby. The medicines most effective in affording relief are those which lower the activity of the reflex function—notably chloral, bromide of potassium, etc. These facts indicate that an exaltation of the reflex function of the spinal cord is caused by strychnine. But this is probably not alone sufficient: irritation of the motor cells is also a factor (Spitzka). In opposition to the commonly accepted view, Falck maintains that strychnine acts primarily on the brain, or rather on the vaso-motor center of the brain, then on the inhibitory center for the heart, and the respiratory center, and lastly on the reflex apparatus of the cord. The spasms are the combined results of these actions.

Bernard held that the sensibility of the sensory nerves is destroyed by strychnine, but after the motor functions have ceased. Martin-Magron, and subsequently Vulpian, ascertained that the sensibility persists after motility has ceased. This contradiction of supposed facts has been examined more recently by Busch, whose observations, if entitled to belief, support the statement of Bernard. Busch has found that the toe of the poisoned frog may be crushed, and the central portion of the divided sciatic may be burned, without inducing spasms or reflex movements, when the slightest jar of the animal will cause strong convulsions. Kölliker and Vulpian, with many others, hold that the excitability of the motor nerves is so far impaired by strychnine that irritation of the nerve-trunk produces very feeble or no muscular contractions. The American observers Klapp and Spitzka both maintain that the peripheral nerves are unaffected in strychnine poisoning. Martin-Magron et Buisson and Vulpian find that the action of strychnine is local on the nerves, and is therefore greatly influenced by the quantity of the poison reaching them. If the dose of strychnine is small, the motor and sensory nerves remain unimpaired; but if the dose be large, their irritability is destroyed. The influence of the quantity administered is consequently very great, and is exhibited in other respects. Thus, while a merely lethal dose causes strong convulsions, a very large toxic dose will kill at once without any reflex disturbances. It is impossible, then, to make the distinction between motor and sensory nerves as respects the action of strychnine: it either destroys or spares the excitability of both.

While strychnine exalts the irritability of the reflex motor center, it stimulates the vaso-motor center or centers in the cord, with the result of greatly increasing the blood-pressure. This rise in blood-pressure is prevented by dividing the cord, according to Mayer, Klapp, and others, but, according to Schlesinger, not. Now, as it has been found by Richter, who has studied the circulation in transparent parts, by Mayer, and by Spitzka, that the arterioles strongly contract under the influence of strychnine, the blood-pressure must rise from this cause; hence, the observation of Schlesinger is probably correct, that the blood-pressure rises in strychnine-poisoning, notwithstanding division of the cord. As has been tersely expressed by Spitzka, "its vaso-motor effect is to increase the blood-pressure and the rapidity of the blood-current by contracting the arterioles. This effect is independent of the central nervous system." The effects of strychnine on the heart differ in cold- and warm-blooded animals, according to most authorities, and decidedly, also, according to the size of the dose. On frogs, the diastolic pause is prolonged, and the force of the systole augmented, so that arrest of the heart's action may take place in tetanic rigidity. These results, Spitzka holds, are due to an action on the cardiac ganglia and on the pneumogastric. The previous observations of Heinemann, however, do not correspond, for he finds that these phenomena are produced after the vagi are divided. In warm-blooded animals the heart's action is accelerated, while the tension is raised. Klapp, however, finds that strychnine slows the pulse in the cat and rabbit, and that the retardation is due to an impression on the cardiac motor ganglia, and not to stimulation of the inhibition. He finds that the action is the same on both classes of animals. These contradictions are probably due to the difference in the dose employed. A large toxic dose of strychnine will paralyze, instead of stimulate, the vaso-motor center in the medulla, and thus prevent any rise of blood-pressure. A small, merely lethal dose will stimulate the cardiac ganglia, the pneumogastric, and the vaso-motor ganglia; but a large toxic dose will slow the heart, paralyze the vagi and the accelerator apparatus, and depress the vaso-motor functions generally. In the course of annual experiments for class instruction, the author has constantly observed the difference in results due to the quantity administered.

From clinical observation, in the absence of any experimental evidence, strychnine has been ascertained to have a stimulating effect on the respiration. If the dose is less than sufficient to tetanize, the function of respiration is increased in energy and in depth. Hence, this agent antagonizes the respiratory poisons, as well as those morbid states which depress the respiratory function.

On the blood, the experiments of Harley show, strychnine has some action. Agitation of blood with the air, in the presence of strychnine, is followed by a less production of carbonic acid than if strychnine be not present, but such experiments are entitled to small consideration. Strychnine, as Hippel and Cohn have shown, stimulates the retina and increases the sharpness of definition and the area of the visual field. These facts explain the curative effects of strychnine in certain diseases of the retina.

Very peculiar phenomena have been observed by Spitzka as a result of chronic poisoning—an entirely new subject. It appears to be exceedingly difficult to keep animals alive, but Spitzka succeeded in maintaining five frogs in tetanus for over forty days. Symptoms occur under these circumstances quite distinct from those produced in acute poisoning by strychnine. Disease in the cord is set up, "partly as an insular sclerosis, partly as an hemorrhagic or non-haemorrhagic myelitis." These experiments demonstrate that, to maintain a constant effect by strychnine in the beginning, the dose must be increased, but later the quantity given may be decreased and administered at longer intervals. The importance of these observations from the therapeutical point of view is, indeed, great. The symptoms occurring from chronic poisoning are, as respects the spasms, a diminution of their energy, the development of an ataxic state, with tremors and pupillary myosis. These phenomena approach those produced by picrotoxin, and are intermediate between the effects of strychnine proper and of curara or methyl strychnium.