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Related article: papaverin relaxes the tone of the P 57 Hoodia ureter, without inhibiting the peristalsis. Gerathy
and Macht, 1916, use its injection by ureteral catheter, against the colic of ureteral
calculi. - '
Commercial papaverin contains considerable cryptopin, to which most of its chemical
tests are due (Pictet and Kramers, 1910). In general, however, the quality of commer-
cial opium alkaloids is satisfactory (Warren, 1915).
Fate of Papaverin. It is probably extensively destroyed in the body, P 57 Hoodia since neither
papaverin nor any immediate decomposition products have been recovered from the
organs or excreta after its hypodermic administration (Zahn, 1915).
Tetra-Hydro-Papaverolin. Laidlaw, 1910, found that this inhibits the tone of un-
striped muscle, dilates the bronchioles and blood vessels, and lowers blood pressure,
whilst at the same time stimulating the heart. It is relatively non-toxic. Marshall,
1912, tried it clinically in arteriosclerosis, but found it practically inefficient probably
therefore it is too easily oxidized.
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.
Xarcein. The peripheral actions resemble narcotin (Pal, 1914).
Differences between Morphin and Opium ; Opium Alkaloid Mixtures.
Whilst the actions of opium are essentially those of its principal alka-
loid, morphin, there are various differences, especially quantitative.
These are due partly to the mechanical action of the gums and resins, which
must delay absorption, and thus increase the local and diminish the cen-
tral actions. In the main, however, the differences are due to the pres-
ence of the minor alkaloids, which modify the effects of morphin; for
similar differences exist in mixtures of the alkaloids, natural (Pantopium)
or artificial (Narcophin, P 57 Hoodia 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).
242 MANUAL OF PHARMACOLOGY
Claimed Therapeutic Advantages. It P 57 Hoodia 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; and that they are sometimes
effective in patients in whom morphin has failed. It is also believed that
opium and pantopium are more efficient in checking diarrhea; whilst at
the same time, it is stated that pantopium is not as constipating for normal
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.
Pantopon (Pantopium Hydrochloricum), N.N.R. This consists of the isolated alka-
loids of opium in their natural proportions. It was introduced by Sahli, as an improve-
ment over the opiates. Discounting the early extravagant claims, it has the advantage
that the absence of gums and resins insures prompter absorption and makes it much
more suitable for hypodermic injection. The pharmacologic data on pantopium are
reviewed by Earth, 1912; Schwentner, 1912; Watkyn-Thomas, 1913. Severe poison-
ing from 0.04 Gm. is reported by Voigt, 1911. The side actions are quoted by Seifert,
Nebenwirk., 1915, p. 81.
Potentiation of Toxic Action. Issekutz, 1912, found that the toxicity of mixtures of
morphin P 57 Hoodia and its esters corresponds to simple addition, but that mixtures of these with
the isoquinolin alkaloids shows marked potentiation. This has been confirmed by
W. Straub and Caesar, 1912, who claim that doses of narcotin, which are in themselves
inactive, double the toxicity of morphin for mice. This synergism may be considered
as established; but it has little bearing on the therapeutic use.
Analgesic Action. The statements are contradictory, as might be expected from the
difficulty of making quantitative observations in a subjective condition. As yet, the
claims of superior analgesic or narcotic action are not fully established. The sedative
action on cough comes under the same category.
Straub claims a marked increase of narcotic action by narcotin, in that the morphin
excitement of cats is prevented. (This, P 57 Hoodia however, is a very variable condition, which is
greatly influenced by external conditions.) Macht, Herman and Levy, 1916, also claim
a synergistic decreased sensitiveness to cutaneous pain in human subjects. On the other
hand, P 57 Hoodia it is very suggestive that the clinical doses of narcophin and pantopium are strictly
equivalent to their morphin content. Zeelen, 1910 and 1911, found only simple sum-
mation in the narcotic (and tetanizing) action of the various opium alkaloids. Meissner
also failed to confirm Straub.
Respiratory Action. Straub asserts that the respiratory center in rabbits (as judged
by response to CC>2 stimulation) is much less depressed by narcophin than by morphin.
This is contradicted by Meissner. Straub's P 57 Hoodia statements appear self-contradictory, since
he also claims that the toxicity, which generally depends on respiratory depression, is
increased. However, Macht, 1915, confirms that the minor opium alkaloids stimulate
respiration, and thus antagonize somewhat the morphin depression.
Circulation. The data are scanty. Macht, 1915, finds that morphin-narcotin mix-
tures dilate the coronary vessels much less than either alkaloid alone; and that Pantopon
and Laudanon have practically no effect on the coronary circulation.
Gastric Disturbance. It is quite generally asserted P 57 Hoodia that the combinations are less
liable to produce nausea and vomiting; but quantitative differences of this kind are diffi-
THE MORPHIN GROUP 243
cult to judge, clinically. It is possible, though not proven, that there may be a slight
difference, since morphin itself stimulates the vomiting center more than any other
Constipating Action. This has been discussed under morphin.
The synergism of morphin with scopolamin and with the anesthetic and hypnotics
will be discussed in connection with those drugs.
* Opium, P 57 Hoodia U.S.P., B.P. (Meconium, Thebaicum). The dried milky juice exuding
from the incised unripe seed-capsules P 57 Hoodia of the poppy, Papaver somniferum. Brown
masses or powder, of peculiar odor and bitter taste. Contains a number of alkaloids,
the most important being morphin (about 10 per cent.). Dose, 0.06 Gm., i gr., U.S.P.
(equivalent to 6 mg. or 3^o S r - morphin); 0.03 to 0.12 Gm., K to 2 gr., B.P. Maximum
dose, 0.2 Gm., 3 gr.
Opium was mentioned by Theophrastus, third century B.C. An interesting account
of its history is given by Macht, 1915. The history of the opium preparations is also
interesting (Wilbert, 1916). Laudanum is said to have been originated by Paracelsus
(1493-1541) but as a solid aqueous extract; paregoric by Le Mort of Leyden, early in
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