This section is from the book "Materia Medica And Therapeutics - Vegetable Kingdom", by Charles D. F. Phillips. Also available from Amazon: Materia Medica And Therapeutics: Vegetable Kingdom.
(a) Narcotic Action of Morphia. - Of the various constituents of opium, there can be little doubt that morphia most nearly represents the aggregate toxic powers of the drug. In poisonous doses it congests the cerebral vessels, producing coma; it paralyzes common sensation, and, in a less degree, voluntary motion; it paralyzes the muscular coats of the intestines and the bladder, and generally produces death by paralysis of respiration, or, in a word, by apncea. It possesses, moreover, in a high degree, the less conspicuous power of opium (usually referred exclusively to the action of thebaine), of producing convulsions, either clonic or tetanic. In this last respect even the illustrious Claude Bernard does not appear to have been fully aware of the activity of morphia. In estimating the relative power of the different opium-salts as tetanizers, he places morphia only fifth; in a position inferior, that is, not only to thebaine, but to papaverine, narcotine, and codeia. There is the best possible reason to think that in this view Bernard was mistaken. Very numerous records of accidental and criminal morphia-poisoning show that tetanic spasm is really quite as frequent a symptom in the human adult as clonic convulsions are in the child. Dr. Anstie has also shown,1 by experiments on such various animals as dogs, cats, rats, rabbits, guinea-pigs, and frogs, that every variety of abnormal muscular action can be produced by morphia; the most characteristic, however, being cataleptic rigidity, shown in the rat, and tetanus, shown in the frog. But indeed there are other strange anomalies in this comparative table of Bernard's. In particular, he actually reckons narceine as superior to morphia in hypnotic power. This is so exceedingly incorrect (as will presently be seen) as to shake our confidence in these experiments, great as is Bernard's reputation.
(b) Narcotic Action of Codeia. - The action of poisonous doses of codeia has been mainly established by the researches of Wachs,2 Baxt,3 Fraser, and Crum-Brown4 upon brute animals. On men there has been no opportunity of observing any but those minor poisonous effects which are produced by a somewhat excessive medicinal dose. The general result seems to be that the narcotic influence falls most severely on the cerebellum and medulla oblongata, producing convulsions. Wachs, who experimented on a large series of animals (under the direction of Falck), observed, in rabbits and dogs, the following general train of symptoms: muscular tremors, a sudden shriek, and stretching out of the limbs; twitching of the lips, and jerking of the eyeballs; (occasionally spasms of the jaw-muscles, and backward locomotory movements, or running in a circle;) weakness of the limbs, restlessness, projection of the eyeballs, immediately followed by opisthotonos and inspiratory spasm, which was rapidly fatal if the dose was very large, but with rather smaller doses, repeated at intervals, was varied by clonic spasms, ending in exhaustion and death. The whole suite of phenomena much resembled those produced by picrotoxine. After death, Wachs usually found very pronounced hyperemia of the cerebral membranes; and in dogs there was also much fluid collected in the ventricles. The substance of the brain seems to have been always uniformly free, both from hyperaemia and from local haemorrhage. The heart was always greatly distended by dark blood; the lungs were greatly congested, as were the liver, spleen, and kidneys; while the alimentary canal, the urinary bladder, and the pancreas were anaemic; the gall-bladder was excessively full.
The minor poisonous effects, as noted in human beings, are semi-coma instead of sleep, nausea, vomiting, severe pain in the stomach, sometimes tinnitus aurium, slight salivation, feeling of pressure in the temples, weakness of sight, and a somewhat remarkable slowing of the pulse.
(c) Narcotic Action of Narceine. - Scarcely any salt that exists has given occasion for such disputes and contradictions, respecting the extent of its physiological activity, as narceine. By Claude Bernard it was pronounced the first among the opium-salts as a hypnotic, but as regards tetanic action the least active of them all, and as regards general narcotic action only fourth, but still more active in this way than either morphia or narcotine. At the other extreme, Fronmuller declared, as the result of his experiments, that narceine has no activity whatever; that out of 22 cases in which he gave it, either subcutaneously or by the mouth, in one only was there a doubtful appearance of hypnotic effect; and, on the whole (since there was not a single instance of characteristic narcotic action upon the pulse, the temperature, the pupils, etc.), Dr. John Harley also expressed himself 1 as entirely sceptical as to the poisonous activity of narceine when pure; he had invariably found that any such power which might appear to belong to a particular specimen, was really due to its being contaminated with some of the other alkaloids of opium. Eulenburg, who is in general a very trustworthy witness, states, as the result of his experiments with narceine (prepared by Merk), that this alkaloid must be given in doses twice as large as those of morphia, in order to produce narcotic effects corresponding with those of the latter. Bouchardat (fils) considers2 that the most important physiological effects are dryness of the mouth, nausea, and vomiting; (diarrhoea when as much as 1 to 1 1/2 grains is subcutaneously injected;) subcutaneous twitchings, and slowing of the pulse and respiration. Reviewing the whole matter, it must be allowed that much doubt hangs over the action of narceine, and must continue to do so until the final clearing up of the essential question whether a pure specimen of the alkaloid has ever produced the special effects which are supposed to characterize this agent. On the whole, it seems most probable that although mistakes have been made by certain observers, through employing an impure specimen, this cannot explain such results as those obtained by Eulenburg, who experimented with the carefully prepared narceine of Merk.