The liberation of histamine by certain organic bases / by F.C. MacIntosh and W.D.M. Paton.

  • Paton, William D. M.
Date:
[1949?]
Catalogue details

Licence: In copyright

Credit: The liberation of histamine by certain organic bases / by F.C. MacIntosh and W.D.M. Paton. Source: Wellcome Collection.

    2/32 (page 191)
    11 in irrrn KESULTS Experiments with licheniformin Our first experiments were made with preparations of 'licheniformin hydro¬ chloride5 supplied by Dr R. K. Callow. The material so designated appears to be a mixture of basic compounds of predominantly polypeptide nature (Callow & Work, 1948). The preparations used by us were probably not of identical composition, but they were qualitatively similar in action. The delayed depressor effect. In a cat anaesthetized with chloralose, the first effect on the arterial pressure of a small intravenous dose (e.g. 1-2 mg./kg.) of licheniformin hydrochloride is a rapid fall which closely resembles that produced, for instance, by a small dose of histamine (Fig. 1). But whereas the depressor effect of substances such as histamine or acetylcholine becomes evident a few seconds after the injection, that of licheniformin always has a longer latency, usually about 20-25 sec. Once it has begun, however, the fall in blood pressure with licheniformin may be just as rapid as with hist¬ amine. The depressor effect of such a dose of licheni- j Cat> chioraiose: blood formin is sometimes transient, but more often the pressure. Hist., injection of initial level of blood pressure is not regained for several minutes. With a somewhat larger dose (e.g. 4 mg./kg.) the fall of arterial pressure is more severe and prolonged, and a yet higher dose (e.g. 10 mg./kg.) produces lasting circulatory shock; but the characteristic delay in the appear¬ ance of the depressor effect is still observed whatever the amount injected. In the cat anaesthetized with ether, or decerebrated, licheniformin sometimes causes a small immediate fall of blood pressure, which is followed by, or merges into, a steeper fall occurring after the usual latency. The depressor action of licheniformin is unaffected by atropinization or by section of the vagi. The heart rate is initially unaffected, though cardio- acceleration, presumably reflex or due to circulating adrenaline, may be seen during the recovery phase; and the heart continues to beat strongly even when the blood pressure has been reduced to a low level by a large dose of licheni¬ formin. That the site of the depressor action is predominantly the peripheral vessels is readily shown. The fall of arterial pressure is accompanied by an increase in limb volume (Fig. 2); and when the drug is injected alternately into the right and left auricle, the fall in blood pressure is somewhat greater in the latter case, and begins 2-3 sec. earlier (Fig. 3). In the cat the depressor effect of a small dose of licheniformin is reproducible only if the injections are spaced 10 min. or more apart. With more frequent injections, the second usually evokes 0-2 p,g./kg. of histamine. Lich., injection of 0-95 mg./ kg. of licheniformin hydro¬ chloride.