An alkaloid contained in opium. It is probably methyl-morphine. Morphine = C17H18NO2(OH); codeine = C17H18NO2 (OCH3).

Characters. - In colourless or nearly colourless octahedral crystals. The aqueous solution has a bitter taste and an alkaline reaction.

Preparation. - It is separated from the ammoniacal liquors from which morphine has been obtained, by evaporating, treating the residue with water, precipitating with caustic potash, and purifying the precipitated alkaloid by recrystallisation from ether.

Solubility. - It is soluble in eighty parts of water and of solution of ammonia, readily soluble in spirit and in diluted acids.

Reactions. - The alkaloid dissolves in sulphuric acid, forming a colourless solution, which, when gently warmed with molybdate of ammonium or a trace of perchloride of iron, assumes a deep blue colour, Moistened with strong nitric acid it becomes yellow but not red (difference from and absence of morphine). Ignited in air it yields no ash.

Dose. - For diabetes 1/4 grain gradually increased to 5 grains or more three times a day, unless it produces great drowsiness or the sugar disappears. For cough 1/6 of a grain every three or four hours.

Action. - Codeine has only a slight hypnotic action, and may sometimes be given in doses of 15 grains daily without producing any marked drowsiness in diabetic patients. Others again are rendered drowsy by 5 or 6 grains daily. Its most marked action appears to be on the nerves of the abdominal viscera and on motor centres in the brain. When given for several days it lessens the irritability of the digestive tract so that irritant poisons, like arsenic, produce neither vomiting nor purging.

It increases the irritability of the spinal cord, and produces in frogs languor succeeded by convulsions and paralysis. In mammals it appears rather to stimulate motor centres in the brain (p. 190). It causes some drowsiness, but the motor phenomena are most marked. These are twitchings, manege or swimming movements, paralysis of the hind-legs, and weakened circulation, followed by a sudden shriek and convulsions. Death may occur at once or recovery take place.

I have observed symptoms very like these in poisoning by pure brucine, and in some points they resemble those of picro-toxin (p. 838).

Uses. - Although it is not a powerful hypnotic, like morphine, codeine has been strongly recommended in nervous insomnia, and also in cases where sleep is prevented by the pain of rheumatism or cancer, or by distressing cough. Its power to lessen the irritability of the intestinal nerves has been already mentioned, and possibly it exerts a similar action on the nerves of other viscera, such as those of the respiratory organs, etc. Such an action would explain its beneficial effects in cough when morphine cannot be borne. Its chief use is in diabetes.1 It certainly lessens, and sometimes entirely removes, the sugar from the urine. As Claude Bernard found that irritation of the central end of the cut vagus caused dilatation of the hepatic vessels and the appearance of sugar in the urine, it seems not improbable that the utility of codeine in diabetes is due to its power of lessening the irritability of the afferent fibres in the nerves of the abdominal viscera. This is rendered all the more likely by the fact that codeine does not prevent the occurrence of sugar in the urine in carbonic oxide poisoning,2 where alterations in tissue change, leading to glycosuria, are probably of a more general nature, and less dependent on local alterations in the hepatic circulation.

1 Pavy, Guy's Hospital Reports. 2 The late Otto Schultzen.

Physiological Action of Opium.

General Action. - Opium, and all its alkaloids hitherto examined, act almost exclusively on the central nervous system, and in mammals especially on the brain, the brain-symptoms preponderating in proportion as the organ is developed relatively to the other nerve-centres. This conclusion holds good only for mammals, and must be qualified in regard to the frog, for in it narcotine, codeine, papaverine, and thebaine have also a paralysing action on the motor ganglia of the heart. Opium and its alkaloids agree not only in the organ they affect but in the nature of their action. The symptoms may be divided into two stages: (1) Narcosis, due to a paralytic action on the brain, followed by

(2) Tetanus, due to increased irritability of the spinal cord. Action on Frogs. - If the drug be introduced by injection under the skin of a frog, the functions of the nerve-centres are abolished in the order of their development, the highest centres being first affected (vide p. 183).

The first symptom to appear after the injection of the drug is a diminution of the power of voluntary movement; the. frog remains quiet, making no effort at voluntary movement; but when irritated responds to the stimulation by springing in the usual way. Next, the power of co-ordination is lost; the frog springs as before when irritated, but has no control over the direction of its leaps. It then gradually loses the power of springing in response to stimulation, and finally reflex action cannot be excited. The heart is unaffected.

After a time increased excitability of the spinal cord comes on, so that the slightest irritation causes muscular spasms like those of strychnine-poisoning. During this condition the spinal cord of the frog does not react to stimuli in the ordinary way, but responds as it were by one violent explosion, after which it seems to become exhausted for a time, but after an interval another violent spasm can be induced, so that there are alternating periods of spasm and exhaustion. If the action of the drug be not pushed beyond this point, the phenomena will pass off in the reverse order of their appearance. If pushed further, there succeeds a deepening paralysis, and respiration becomes first slower and then stops.

Action on Birds. - Birds are peculiarly insusceptible to the action of opium or morphine. But morphine produces in them a marked lowering of body temperature, sometimes to the extent of 5° or 6° C.1