146 G. N. STEWAET 



and can be Veil obtained after removal of the suprarenals or suppression 

 of the output of epinephrin from them (Figs. 16 and 17). 



Action of Drugs upon the Epinephrin Output 



Apart from the effects of directly stimulating or dividing the splanch- 

 nic nerves, or other portions of epinephrin-secretory nervous mechan- 

 ism, the one way in which decided changes in the epinephrin output 

 have been unequivocally demonstrated up to the present time has been 

 by certain drugs. Strychnin causes a marked increase in the output 

 (up to 10 or 12 times the initial value). This increase is not transient, 



Fig. 18. Intestine tracings. At 2 and 4. Ringer's solution was replaced by in- 

 different (jugular) blood from a dog, and this at 3 by a specimen of blood from the 

 suprarenals collected before the administration of strychnin; at 5 by a suprarenal 

 blood specimen, collected 3 minutes after strychnin. The blood specimens were diluted 

 with 3 volumes Ringers solution. Although the blood flow for the latter specimen 

 was somewhat greater than for the specimen obtained before strychnin its epinephrin 

 concentration was more than 10 times, greater, as shown by curves not reproduced, and 

 the output of epinephrin was not less than 11 or 12 times the initial output. (Reduced 

 to one-half.) (After Stewart and Rogoff, J. Pharm. d Exper. Therap.) 



but persists for a considerable time. Although no attempt was made to 

 continue the experiments until it had completely subsided, a notable aug- 

 mentation was, as a rule, still found an hour and a half after intravenous 

 injection of the drug, and indeed the action, particularly with the smaller 

 doses, may go on increasing during the experiment. With subcutaneous 

 administration the same effect is produced. Doses of strychnin, probably 

 within the therapeutic range, and which cause little or no exaggeration 

 of reflex excitability, are capable of producing a considerable increase in 

 the rate of output of epinephrin (Fig. 18). In spite of the greatly in- 

 creased output of epinephrin induced by strychnin there is no evidence 

 that the epinephrin store of the suprarenals is distinctly diminished even 

 by the prolonged action of the drug in large and repeated doses. The 



