RT Journal Article
SR Electronic
T1 THE ACTION OF DRUGS UPON THE OUTPUT OF EPINEPHRIN FROM THE ADRENALS I. STRYCHNINE
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 95
OP 166
VO 13
IS 2
A1 G. N. STEWART
A1 J. M. ROGOFF
YR 1919
UL http://jpet.aspetjournals.org/content/13/2/95.abstract
AB 1.The paper begins with a discussion of essential points in the technique of measuring the epinephrin output. It is pointed out that in general it is no more possible to demonstrate (or measure) alterations in the rate of epinephrin output by observations which only take account of changes in the concentration of epinephrin in the blood coming from the adrenals, while ignoring concomitant changes in the rate of the blood flow, than it would be to demonstrate (or measure) alterations in the rate of carbon dioxide production in an organ by observations which only took account of the number of volumes of carbon dioxide in 100 cc. of blood, but paid no attention to the number of cubic centimeters of blood passing through the organ in a given time. In this connection it is again shown that statements in the literature as to the influence of various conditions in notably augmenting the rate of epinephrin output are vitiated by neglect of this factor. 2. Strychnine causes a marked increase in the output of epinephrin from the adrenals (in the dog and cat). Although it is only by chance that a sample of adrenal blood corresponding to the maximum increase can be collected, outputs ten times the original output have been observed. 3. The increase is not transient but persists for a considerable time. No attempt was made to continue the experiments until it had completely subsided, as it was not thought that any useful purpose could be served by keeping the animals, after the necessary operation, several hours under the anesthetic. The last adrenal sample was usually taken an hour to an hour and a half after the strychnine injection and it was the rule to find that at this time the epinephrin output was still notably augmented. Indeed, with the smaller doses the effect may go on increasing during the whole experiment and the last specimen may correspond to a rate of output as great as or greater than that of any previous specimen. Abundant evidence has been produced in other papers that animals under similar experimental conditions, but without strychnine, do not show an increased epinephrin output. 4. No attempt was made to fix a minimum effective dose but it was clearly shown that doses of strychnine well within the therapeutic range, and which caused little or no exaggeration of reflex excitability are capable of producing a considerable augmentation in the rate of output. In this connection it must be remembered that the animals were necessarily well anesthetized, and it is to be supposed that still smaller doses would suffice in non-anaesthetised animals. 5. Indications were obtained in some experiments that the stage of prolonged augmentation of the rate of output, which constitutes the principal action of the drug, may be preceded by a transient diminution. This phenomenon was best seen with the smaller doses and with subcutaneous administration of the drug, presumably because with the larger doses and with intravenous injection the augmentation of the output comes on so rapidly as to mask any preliminary decrease. 6. The augmentation of the output caused by strychnine is associated with a more or less marked increase in the epinephrin concentration, even when at the same time the rate of blood flow through the adrenals has been increased, a phenomenon not seen in the absence of the drug. But no evidence has been found that under the influence of strychnine the possible normal maximum concentration in the plasma (something like 1:500,000 as assayed by rabbit segments in adrenal blood from non-strychninised animals) can be increased. 7. The above conclusions are all based on assays of adrenal blood with rabbit intestine and uterus segments. But corroborative evidence of the augmenting influence of strychnine was obtained by studying the effects produced on the blood pressure by adrenal blood, collected in a cava pocket for a given time before and after strychnine, when the blood was allowed to pass from the pocket into the circulation, and in other ways. 8. In spite of the greatly increased output of epinephrin caused by strychnine, there was no evidence that the epinephrin store of the adrenals is distinctly diminished even by the prolonged action of the drug in large and repeated doses. The accumulation of epinephrin in the glands is therefore increased as well as its liberation. This is what happens during stimulation of the splanchnic except when intermittent stimulation is continued for very long periods. It corroborates other evidence that the strychnine effect is produced by an intensification of the secretory process through the nervous mechanism which normally governs it. There is no direct action on the glands.