1 "Stimulants and Narcotics." London, 1864. 2 Das Codeia. Eine Monographie. Marburg, 1868. 3 Virchow's Archiv, 1869.

4 "On the Connection between Chemical Constitution and Physiological Action." Edinburgh, 1868.

(d) Narcotic Action of Papaverine. - Respecting this alkaloid also there have been great disputes, but the researches of Baxt3 have placed it beyond doubt that papaverine is a narcotic of considerable power in paralyzing the heart (independently of any action of the vagus), and in paralyzing the function of reflex irritability, besides possessing a hypnotic action, which will be considered under the heading "Therapeutics."

(e) Narcotic Action of Narcotine. - This alkaloid likewise possesses decided narcotic qualities when given in large doses. The latest and most trustworthy researches are those of Baxt and of Kauz-mann. The former concludes that the poisonous action of narcotine is very analogous to that of thebaine, but attended by less convulsion, and by more of absolute paralysis. Kauzmann destroyed a cat with about five grains. Symptoms commenced in four hours with tremors, tetanic rigidity of the extremities, contraction of the pupil, clonic spasms of half a minute to a minute's duration, succeeded by coma and death in 36 hours. Claude Bernard, while placing narcotine among those opium-alkaloids which are exciters of convulsion, considered it the least poisonous of all opium-salts; and this opinion must probably be correct, considering the quantities of narcotine which have been given in India as anti-periodic medicines by O'shaughnessy and others.

1 Practitioner, 1868.

2 De la Narceine. These de Concours. Paris, 1865.

3 Virchow's Archiv, lxx., 1869.

(/) Poisonous Action of Thebaine. - This alkaloid, which is the most poisonous of the opium-salts, has an action much resembling that of strychnia. It is a powerfully tetanizing narcotic. The most complete observations are those of F. W. Muller,1 who experimented upon frogs, dogs, rabbits, and pigeons. The last-named were found to be more re-sistent than the others. In dogs and rabbits tetanic spasms set in within a few minutes (preceded in rabbits by general restlessness), and this was followed by paralysis. In pigeons, with fatal doses, there was general tremor of the whole body, and then a strong tetanic attack, followed by isolated spasms and a paralytic condition. Where recovery took place there was vomiting, and either general tetanus or only partial tonic spasms. From experiments made upon frogs' hearts removed from the body, Muller concluded that thebaine acts partly as a direct poison to the heart; if the heart be immersed in a weak aqueous solution of thebaine its beats diminish, and it comes to a stop more rapidly than if plunged in pure distilled water. Muller decided a question of much interest in regard to the explanation of the physiological action of opium itself. He showed that morphia and thebaine do not antagonize each other; for a mixture of the two, subcutaneously injected into a rabbit, caused death of a kind similar to that produced by thebaine, and with great rapidity. No therapeutic application of thebaine has yet been made.

Therapeutic Action of Opium. - As a Hypnotic, opium is the best and most trustworthy of drugs, with the solitary exception of hydrate of chloral, the only medicine which in this respect approaches it. In former times there was remarkable failure of appreciation of the circumstances under which its soporific influence should be sought, and of the doses most appropriate for the purpose. When opium is given in such a manner as to produce sleep (in a previously healthy person) in the best way, its action is very peculiar. The patient, in about fifteen to thirty minutes after taking the medicine, perceives first a slight sense of muscular languor and relaxation in all parts of the body; and to this is soon added a not unpleasant sense of slight fulness and weight at the back of the head. The vague discomfort which had before pervaded the system, now gives way to a feeling of perfect lightness and freedom; and the mental state is that of agreeable indifference to everything, without any approach to stupor. After this condition has lasted for a variable time, drowsiness, such as precedes healthy sleep, comes on, and the patient soon sinks into slumber. On awakening he feels refreshed, and there is no nausea, and only a very little furring of the tongue, nor is there any headache. Very often, however, the next action of the bowels is slightly delayed, and, when it occurs, is somewhat constipated from extra dryness of the faeces. Such effects are commonly produced by half a grain to a grain of opium, or its equivalent in tincture, etc.

Very different is the result when marked wakefulness is treated by the administration of a heavy dose, such as two to five grains; then, as above remarked, the patient is truly narcotized. The early symptoms are those of semi-delirium; if sleep occurs, it is opium-coma rather than genuine sleep, and on waking, the patient experiences the nausea, headache, and constipation (with absence of bile from the stools) which indicate the receding stages of a real (though slight) opium-poisoning.

1 "Das Thebain; eine Monographic" Marburg, 1868.

There are curious differences, as yet not at all fully explained, between the hypnotic effects of different preparations of opium. Laudanum fairly agrees in action with opium per se; the only differences depending, apparently, on slowness of solution of the latter in the stomach and consequent slowness of its absorption. On the other hand, the well-known "liquor opii sedativus" of Battley, and the preparations by which that medicine is most successfully imitated, contain about 50 per cent. more opium than simple laudanum,1 but are generally admitted to produce a much more tranquil hypnotic effect, with less of brain-excitement at the commencement, and less of unpleasant after-consequences. So also the "black drop" and the "acetum opii" of the old Dublin Pharmacopoeia. These, however, were much stronger preparations than laudanum; and are now nearly gone out of use. The "extractum liquidum" of the present (British) Pharmacopoeia is the officinal representative of the kind of preparation which was sought for in Battley's liquor, but is one-seventh stronger than the tincture.