This section is from the book "Materia Medica: Pharmacology: Therapeutics Prescription Writing For Students and Practitioners", by Walter A. Bastedo. Also available from Amazon: Materia Medica: Pharmacology: Therapeutics: Prescription Writing for Students and Practitioners.
Fig. 36. - Kolliker's schema to show the reflex arc. A shows the posterior root-fiber (black) dividing and spreading up and down the cord, and connecting with many motor cells (red) through its synapses (black ramifications). B shows the posterior root-fiber connecting through the first synapse of the afferent system with an intermediate neuron (green), which in turn connects with numerous motor cells (red) through its synapses (after Howell).
Sherrington"s Theory. - As has been pointed out, a certain stimulus leads, normally, through coordination, not only to contraction of a certain group of muscles, but also to relaxation of the opposing group; and the same stimulus, after a toxic dose of strychnine, induces contraction not only in the usual group, but also in the antagonists. Therefore, under strong strychnine stimulation all the muscles contract, so that, of two sets of opposing muscles, the stronger regularly predominate. For example, if an animal poisoned with strychnine attempts to open its mouth, both the opening and closing muscles are excited, and as the closing muscles are the stronger, the mouth becomes all the more tightly closed. If a man under an excessive dose of strychnine tries to walk, his gait is spastic, and his legs are more or less stiff, because all the muscles are in an excitable contractile state. Sherrington's belief is that the strychnine overaction is due to a change of the usual relaxation or inhibition of the opposing muscles into contraction or excitation, and the will is in complete abeyance. This well explains the exaggerated and convulsive reflexes, and the spasticity, but not the widespread response to a stimulus.
Following up this theory, Bayliss has been able to show that, after poisonous amounts of strychnine, stimulation of the depressor nerve will result in a rise in arterial pressure, i. e., the depressor nerve is no longer an inhibitory nerve, but an excitatory nerve.
Tone is a condition of readiness to respond to stimulus. All the muscles, both voluntary and involuntary, are in a constant state of tone, i. e., they are in a condition of slight contraction, so that they are drawn up in readiness to work the moment a stimulus comes. One or two experiments to determine the nature of muscular tone are of interest:
1. If a frog is decapitated and the sciatic nerve of one side cut, the leg on the cut side is more relaxed than the other leg, i. e., severance of the leg from its connection with the central nervous system results in greater relaxation than normal, or loss of its tone. It is evident then that the tone of the leg is due to the reception of stimuli from the motor cells of the spinal cord.
2. If a frog's skin is anesthetized by immersing the frog in 5 per cent. cocaine to cut off external stimuli, or its posterior nerve-roots cut to prevent any afferent impulses from reaching the cord, there results marked muscular relaxation, i. e., loss of tone on both sides. Evidently, therefore, tone of voluntary muscle is, at least in great part, dependent upon the reception in the cord of afferent impulses. Tone is, therefore, largely a manifestation of reflex activity. Strychnine heightens tone by increasing reflex excitability, and on this property most of the therapeutic usefulness of strychnine depends. It is the best of our genuine "tonics."
The therapeutic use of strychnine is to open up the normal paths in the cord when they become clogged, so that an afferent impulse can reach the usual motor cells with greater facility. In other words, it is to increase tone and the usual purposeful reflexes. Therapeutically, there is no desire to have an impulse affect other cells than the usual ones. The poisonous action is - (1) To open widely the regular paths to motor cells (overtone); (2) to interfere with coordination by changing the normal inhibition of opposing muscles into excitation (spasticity); and (3) to open up great numbers of new paths, so that an impulse can reach and excite large numbers of motor cells that are ordinarily beyond its influence (general spinal convulsions).
Fig. 37. - Strychnine sulphate, 0.2 mg. per kilo, no effect on circulatory organs. Upper tracing, auricle; middle, ventricle; lower, blood-pressure; upper line of 6gures, pulse-rate. (Traning made by Dr. C. C. Lieb.)
There is no effect in man. In the frog large quantities may depress the ends of the vagus nerves and of the sensory and motor nerves; and in animals in which strychnine convulsions have been prevented by spinal analgesia, a curarelike effect on motor nerve-endings has been suspected.
In their action upon the central nervous system caffeine and strychnine are stimulants of the same class. But caffeine affects the cerebrum most, while strychnine acts most upon the spinal cord. Both stimulate the medullary centers more or less. Pilcher and Sollmann state that from doses large enough to be dangerous strychnine is "usually without action on the vasomotor center, but occasionally may stimulate the center moderately."
No direct action, though improved muscular power results from increased tone and heightened reflex activity.
In perfusion of the isolated heart, only high concentrations of strychnine have any effect, so the heart muscle is not stimulated by any dose that would be given to man. In perfusing an isolated viscus or limb there is no effect upon the arteries. In the intact mammal, after therapeutic doses, there may be a slight slowing of the pulse from a moderate stimulation of the vagus center, and a slight rise of arterial pressure from stimulation of the vasoconstrictor center, but, as a rule, the effect on blood-pressure is very slight, if any. In cases of general weakness the improvement in general muscular tone may have a good effect upon the circulation, but it is a mistaken idea among physicians that strychnine is a direct stimulant to the heart.