Effects of Intravenous Injection of Suprarenal Extracts 65 



excitation). Therefore, if, as sometimes happens, both contraction and 

 inhibition can normally be brought about through the sympathetic and 

 also by adrenalin, when the contraction effect is abolished by ergotoxine, 

 the inhibition effect alone appears, and this may produce a reversal of the 

 normal action. Thus after a sufficient dose of ergotoxine, adrenalin pro- 

 duces vasodilatation in place of vasoconstriction, and inhibition of uterine 

 contractions instead of increased contraction. In the ferret the urinary 

 bladder is contracted by suprarenal extract if ergotoxine is previously 

 administered (Elliott), although it is usually inhibited. This corresponds 

 with the effect of administering the same drug prior to stimulating the 

 sympathetic nerves passing to that viscus. Ergotoxine doubtless acts, like 

 adrenalin, on the juiictional or receptive substance. Dixon obtained like 

 results with apocodeine. 



The action of adrenalin upon the terminal apparatus of the sympathetic 

 system is common to a number of primary and secondary amines: the 

 action has been termed sympatho-mimetic by Barger and Dale. The 

 more nearly the structure of the amine approaches that of adrenalin the 

 more marked is this action. A knowledge of these facts has led to the 

 production of various synthetic drugs having similar properties. The 

 chemical history of adrenalin furnishes, indeed, a striking illustration of 

 the drug-like character of autacoids. 



Repeated intravenous injections into the ear- vein given at intervals of 

 a few days produce (in the rabbit) degenerative sclerosis of arteries (Josue). 

 This action is not specific to the suprarenal autacoid, but is the result of 

 prolonged abnormally high blood-pressure, however produced. 



Applied directly to the smaller blood-vessels, the suprarenal autacoid 

 produces marked contraction of the muscular coat, and it is therefore of 

 value in surgery as a styptic for arresting haemorrhage from small arteries. 



It was found by Oliver and myself (and confirmed by other workers) that 

 the contractions of skeletal muscle are prolonged under the influence of suprarenal 

 extract. The effect we obtained must, however, have been due to something in 

 the extract used other than adrenalin, for I have since failed to get any effect 

 with small doses of that substance. In larger doses adrenalin has a paralysing 

 action on muscle somewhat similar to that produced by excess of potassium salts 

 (Takayasu). Nevertheless, administration of suprarenal by the mouth has been 

 shown to be favourable to muscular action, fatigue being less easily produced : this 

 was found by Langlois to be the case in Addison's disease (fig. 42). Lucien and 

 Parisot find postponement of fatigue in frog muscle to be an effect of the autacoid. 



Effects of Subcutaneous and Buccal Administration. Subcutaneous in- 

 jection of the extract does not produce the rapid effect on involuntary muscle 

 which is so characteristic of intravenous injection although, as Meltzer and 

 Auer have shown, intramuscular injection may show this result. But large 

 doses of the extract, or of the separated autacoid substance of the medulla, 

 produce in rabbits and some other animals serious or even fatal symptoms. 



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