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.
1 Marshall Hall, Memoirs on the Nervous System, p. 7 (London, 1837). Wit-kowski, Archiv fur exper. Path. und Pharm., Band vii. p. 247.
Ammonium bromide also causes, first, complete loss of voluntary movement and reflex action, but at a later stage in the poisoning convulsions.
On the hypothesis of interference, the phenomena produced both by atropine and by morphine can be more simply explained. These drugs, acting on the nervous structures, gradually lessen the functional activity of the nerve-fibrils which connect the nerve-cells together; the impulses are retarded, and thus the length of nervous connection between the cells of the spinal cord, which is calculated to keep them in proper relation in the normal animal just suffices at a certain stage to throw the impulses half a wave-length behind the other, and thus to cause complete inhibition and apparent paralysis.
As the action of the drug goes on, the retardation becomes still greater, and then the impulses are thrown very nearly, but not quite, a whole wave-length behind the other, and thus they coincide for a short time, but gradually again interfere, and therefore we get, on the application of a stimulus, a tonic convulsion followed by several clonic ones, and then by a period of rest. This explanation is further borne out by the fact observed by Fraser, that the convulsions caused by atropine occurred more readily during winter, when the temperature of the laboratory is low, and the cold would tend to aid the action of the drug in retarding the transmission of impulses.1
The effect of strychnine in causing tetanus is very remarkable; a very small dose of it administered to a frog first renders the animal most sensitive to reflex impulses, so that slight impressions which would normally have no effect, produce reflex action. As the poisoning proceeds, a slight stimulus no longer produces a reflex action limited to a few muscles, but causes a general convulsion throughout all the body, all the muscles being apparently put equally on the stretch. In man the form assumed by the body is that of a bow, the head and the heels being bent backwards, the hands clenched, and the arms tightly drawn to the body.
My friend Dr. Ferrier has shown that this position is due to the different strengths of the various muscles in the body. All being contracted to their utmost, the stronger overpower the weaker, and thus the powerful extensors of the back and muscles of the thighs keep the body arched backwards and the legs rigid, while the adductors and flexors of the arms and fingers clench the fist and bend the arms, and draw them close to the body.1 The convulsions are not continuous, but are clonic; a violent convulsion coming on and lasting for a while, and then being succeeded by an interval of rest, to which after a little while another convulsion succeeds. The animal generally dies either of asphyxia during a convulsion, or of stoppage of the heart during the interval.
1 Transactions of the Royal Society of Edinburgh, vol. xxv. p. 467.
When the animal is left to itself, the convulsions - at least in frogs - appear to me to follow a certain rhythm, the intervals remaining for some little time of nearly the same extent.
A slight external stimulus, however, applied during the interval - or at least during a certain part of it - will bring on the convulsion. But this is not the case during the whole interval. Immediately after each convulsion has ceased I have observed a period in which stimulation applied to the surface appears to have no effect whatever.
It is rather extraordinary, also, that although touching the surface produces convulsions, irritation of the skin by acid does not do so.2
The cause of those convulsions was located in the spinal cord by Magendie in an elaborate series of experiments, which will be described later on (p. 177).
Other observers have tried to discover whether any change in the peripheral nerves also took part in causing convulsion; but from further experiments it appears that the irritability of the sensory nerves is not increased.3
According to Rosenthal, strychnine does not affect the rate at which impulses are transmitted in peripheral nerves; he, however, states that it lessens the time required for reflex actions. Wundt came to the conclusion that the reflex time was on the contrary increased.
In trying to explain the phenomenon of strychnine-tetanus on the hypothesis of interference, one would have been inclined by Rosenthal's experiments to say that strychnine quickened the transmission of impulses along those fibres in the spinal cord which connect the different cells together.
The impulses which normally, by travelling further round, fell behind the simple motor ones by half a wave-length, and thus inhibited them, would now fall only a small fraction of a wave-length behind, and we should have stimulation instead of inhibition.
Wundt's conclusion, on the other hand, would lead to the same result by supposing that the inhibitory wave was retarded so as to fall a whole wave-length behind the motor one. On the as-sumption, however, that the fibres which pass transversely across from sensory to motor cells, and those that pass upwards and downwards in the cord connecting the cells of successive strata in it, are equally affected, we do not get a satisfactory explanation of the rhythmical nature of the convulsions. By supposing, however, that these are not equally affected, but that the resistance in one - let us say that in the transverse fibres - is more increased than in the longitudinal fibres, we shall get the impulses at one time thrown completely upon each other, causing intense convulsion, at another half a wave-length behind, causing complete relaxation, which is exactly what we find.
1 Brain, vol. iv. p. 313.
2 Eckhard, Hermann's Handb. d. Physiol., Band ii. Th. 2, p. 43.
3 Bernstein, quoted by Eckhard, op. cit. p. 40. Walton, Ludwig's Arbeiten, 1882.