(C17H19NO3 = C17H17NO2 + H2O),
and the hydrochlorate of apomorphine is produced. This succeeds when even 1⁄2 mgrm. is heated with 1⁄10 c.c. of strong HCl, and the tests for apomorphine applied.
If concentrated sulphuric acid be digested on morphine for twelve to fifteen hours (or heated for half an hour at 100°), on adding to the cooled violet-coloured solution either a crystal of nitrate of potash or of chlorate of potash, or a drop of dilute nitric acid, a beautiful violet-blue colour is produced, which passes gradually into a dark blood-red. 1⁄100 of a mgrm. will respond distinctly to this test. Fröhde’s reagent strikes with morphine a beautiful violet colour, passing from blue into dirty green, and finally almost vanishing. 1⁄200 of a mgrm. will respond to the test, but it is not itself conclusive, since papaverine and certain glucosides give an identical reaction.
§ 356. Symptoms of Opium and Morphine Poisoning.—The symptoms of opium and morphine poisoning are so much alike, that clinically it is impossible to distinguish them; therefore they may be considered together.
Action on Animals—Frogs.—The action of morphine or opium on frogs is peculiar: the animal at first springs restlessly about, and then falls into a condition extremely analogous to that seen in strychnine poisoning, every motion or external irritation producing a tetanic convulsion. This condition is, however, sometimes not observed. The tetanic stage is followed by paralysis of reflex movements and cessation of breathing, the heart continuing to beat.
Dogs.—0·2 to 0·5 grm. of morphine meconate, or acetate, injected directly into the circulation of a dog, shows its effects almost immediately. The dog becomes uneasy, and moves its jaws and tongue as if some peculiar taste were experienced; it may bark or utter a whine, and then in a minute or two falls into a profound sleep, which is often so deep that while it lasts—usually several hours—an operation may be performed. In whatever attitude the limbs are placed, they remain. The respiration is rapid and stertorous, and most reflex actions are extinguished. Towards the end of the sleep, any sudden noise may startle the animal, and when he wakes his faculties are evidently confused. A partial paralysis of the hind legs has often been noticed, and then the dog, with his tail and pelvis low, has something the attitude of the hyena. Hence this condition (first, I believe, noticed by Bernard) has been called the “hyenoid” state. If the dose is larger than 2 to 3 grms. (31 to 46 grains), the symptoms are not dissimilar, save that they terminate in death, which is generally preceded by convulsions.[381]
[381] MM. Grasset and Amblard have studied the action of morphine in causing convulsions in the mammalia. They found that if small doses of hydrochlorate of morphine (from 1 to 15 centigrammes) are administered to dogs, the brief sleep which is produced may be accompanied by partial muscular contractions (in one paw, for instance), which are renewed at variable intervals. Then occur true convulsive shocks in the whole body or in the hind limbs. After an interval, the phenomena recur in more intense degree, and are followed by true convulsions. Regularly, ten or sixteen times a minute, at each inspiration, the hind limbs present a series of convulsive movements, which may become general. Sometimes they are excited by external stimulation, but they are usually spontaneous. The sleep may continue profound during this convulsive period, or it may become distinctly lighter. These convulsive phenomena may continue, with intervals, for an hour. Differences are observed with different animals; but the chief characters of the phenomena are as described. In certain animals, and with small doses, there may be a brief convulsive phase at the commencement of the sleep, but it is much less constant than the later period of spasm. These convulsions, the authors believe, have not previously been described, except as a consequence of very large doses, amounting to grammes. The period of cerebral excitement, described by Claude Bernard as occurring at the commencement of the sleep from morphine, is a phenomenon of a different order. The conclusions drawn from the experiments are—(1) That morphia is not diametrically opposed to thebaine, as is often stated, since it has, to a certain degree, the convulsive properties of the latter alkaloid. (2) That the excitomotor action of opium cannot be exclusively attributed to the convulsive alkaloids, but is, in fact, due to those which are soporific. According to the ordinary composition of opium, 5 centigrammes of morphine represent about a milligramme of thebaine. But these experiments show that the quantity of morphine has a much more powerful convulsive action than a milligramme of thebaine. (3) There is not the supposed antagonism between the action of morphine on the frog and on the mammalia. (4) The researches hitherto undertaken on the antagonism between morphine and other agents need to be repeated, and a separate study made of the substances which antagonise the convulsive and soporific action.