312 PROFESSOR C. R. MARSHALL ON 



vessels being the cause of the fall of temperature is the appearance of the vessels of the 

 car. These were seen to be dilated when the temperature was falling, and contracted 

 when the temperature was rising. My observations after administering tutin largely 

 confirm those of Harnack with sodium santoninate on this point. Unfortunately my 

 experiments were made before the publication of his paper, and 1 did not pay special 

 attention to this connection, but, where noted, dilatation of the vessels of the ear 

 occurred during the fall and contraction during the rise of temperature. In a few 

 instances the ear vessels were noted to be more contracted before the rise of tempera- 

 ture commenced. 



Effect of Decomposition Products. 



The products of hydrolysis of tutin possess no peculiar pharmacological action. 

 Insufficient hydrolysis yields a product with a variable tutin action dependent upon the 

 undecomposed tutin. 



After heating with excess of 0'2 per cent, hydrochloric acid for fifteen minutes on a 

 water-bath, neutralising with sodium bicarbonate, evaporating, extracting with alcohol, 

 and re-extracting the inspissated alcoholic extract with ether, a colourless syrup was 

 obtained which gave the physiological action of tutin, and from which crystals of tutin 

 separated later. After heating the hydrochloric acid solution on the water-bath for an 

 hour and extracting in a similar manner, a colourless syrup was obtained which did not 

 deposit crystals of tutin, but which caused tutin convulsions after administration. On 

 heating a solution of tutin in 1 per cent, hydrochloric acid on the water-bath for three 

 hours, neutralising and extracting as before, a reddish oil insoluble in water and a 

 brownish substance soluble in water were obtained, but neither produced any 

 physiological effect. The sugar produced by hydrolysis has not been identified. I can 

 corroborate Easterfield and Aston's * statement that it does not form a crystalline 

 osazone. In itself, however, the sugar is of little pharmacological importance. 



Dilute solutions of alkalies appear to decompose tutin much more quickly than 

 dilute acids. A solution of tutin in 0*1 per cent, sodium hydroxide, and one in 0'05 

 per cent, calcium hydroxide, after raising to the boiling-point, cooling, and neutralising, 

 produced no pharmacological action in doses which should have given, if any active 

 principle had been present, a marked result. 



Comparison with other Convulsants. 



The best-known of the substances comparable with tutin are picrotoxin, coriamyrtm, 

 and essence of absinthe. Many others cause convulsions by acting on the brain, but 

 most of them produce other actions not given by tutin. In so far as their convulsant 

 action has been investigated it would seem not to differ materially from that of the 



substances mentioned. 



* Loc tit. 



