mals. When both OH groups arc replaced by acids (heroin) the narcotic action is stronger than for codein, the tetanic action is weaker than with morphin. The constitution of the morphin group of alkaloids is discussed by M. Freund, 1919.
Comparative Activity of the Two Groups.—The alkaloids of both groups are more or less narcotic and convulsant. The essential differences are in the peripheral actions on all kinds of smooth muscle: Their contractions and tonus are stimulated by (he phenanthren group (morphin and its esters), and depressed by the isoquinolin group (papaverin, etc.). This applies to the intestines, bile ducts vas deferens, bronchioles and blood vessels. Macht, 1918, attributes the stimulation to the pyridin radical of the phenanthren group; the depression lo the benzyl radical of the isoquinolin group.
Convulsant-narcotic Series.—In general, the narcotic actions on the brain, on the one hand, and the stimulant action on the cord and medulla on the other, are in inverse ratio; morphin being the most narcotic and least convulsant and thebain the most convulsant and least narcotic; the other morphin esters and the isoquinolin alkaloids being intermediate. Claude Bernard arranged them in the order of: Morphin, codein, narcotin, papaverin, laudanosin, thebain. Buergi, 1914, places them as: Morphin, papaverin, codein, narcotin, narcein, thebain.
Meconic Acid.—This has no effect in the doses which would be administered in opium. Larger doses produce narcosis, muscular fibrillation; medullary convulsions; (uarrbea; curure action (Barth, 1812).
Papaverin.—This is discussed in a seperate section.
Narcotin.—The peripheral actions appear to be similar to papaverin, but weaker (Pal, 1914)—Macht, 1915, found, contrary to Straub, that it is quite toxic to the heart, respiration and other functions.
Narcein.—The peripheral actions resemble narcotin (Pal, 1914).
Differences between Morphin and Opium; Opium Alkaloid Mixtures.
While the actions of opium are essentially those of its principal alkaloid, morphin, there are various diiierences, especially quantitative. These are due partly to the mechanical action of the gums and resins, which delay absorption, and thus increase the local and diminish the central actions. In the main, however, the differences are due to the presence of the minor alkaloids, which modify the effects of morphin; for similar differences exist in mixtures of the alkaloids, natural (Pantopium) or artificial (Narcophin, Laudanons).
The precise differences between the actions of morphin, opium and the mixed alkaloids are still under dispute. The statements of different (and sometimes of the same) observers are so contradictory that it is often impossible to judge them (Literature, E. Buergi, 1914).
Claimed Therapeutic Advantages.—It is asserted that opium and the alkaloid mixtures, for a given degree of analgesic and cough-sedative action, cause less depression of respiration and less nausea; that their action, though slower, is more prolonged. It is also claimed that opium and pantopium are more efficient in checking diarrhea; while at the same time, it is stated that pantopium is not as constipating for normal individuals.
Before considering these actions in detail, it is necessary to describe the nature of the commercial products which have been largely used in the investigations.
Pantopium (Pantopium Hydrochloricum), N.N.R.—This consists of the isolated alkaloids opium in their natural proportions. It was introduced by Sahli. Discounting the early extravagant claims, it has the advantage that the absence of gums and resins prompter absorption and makes it much more suitable for hypodermic injection, The pharmacologic data on pantopium are reviewed by Barth, 1912; Schwentner, 1912; Watkyn-Thomas, 1913. Severe poisoning from 0.04 Gm. is reported by Voigt, 1911. The side actions are quoted by Seifert, Nebenwirk., 1915, p. 81.
