460 Professor Sir Henry E. Boscoe [April IG, 



In considering the historical development of this portion of- his 

 subject, the speaker added that it is interesting to remember that the 

 initiative in the production of artificial febrifuges was given by- 

 Professor Dewar's discovery in 1881 that quinoline, the basis of these 

 antipyretic medicines, is an aromatic compound, as from it he 

 obtained aniline. Moreover, that Dewar and McKendrick were the 

 first to observe that certain pyridine salts act as febrifuges. So that 

 these gentlemen may be said to be the fathers of the antipyretic 

 medicines, as Witt and Eoussin are of the azo-colour industry. 



Kairine, the first of these, was discovered by Prof. O. Fischer, of 

 Munich, in the year 1881, whilst engaged on his investigations of the 

 oxyquinolines. The febrifuge properties of this substance were first 

 noticed by Prof. Filehne, of Erlangen. Kairine is manufactured from 

 quinoline, a basic product derived from aniline by heating it with 

 glycerin and nitrobenzene by the following process. When treated 

 with sulphuric acid, SO4H2, it forms quinoline sulphonic acid, and 

 this when fused with caustic soda yields oxi/quinoline, which is then 

 reduced by tin and hydrochloric acid into tetrahydroxyquinoline, and 

 this again on treatment with OaHgBr yields ethyl-tetraoxyquinoline 

 or kairine. The lowering of the temperature of the body by this com- 

 pound is most remarkable, though, unfortunately, the action is of 

 much shorter duration than that effected by quinine itself ; but on the 

 other hand, with the exception of its burning taste, it exerts no 

 evil effects such as are often observed after administration of large 

 doses of quinine. The commercial article is the hydrochloride, 

 the price is 85s. per lb., and the quantity manufactured has lately 

 diminished owing to the discovery of the second artificial febrifuge, 

 antipyrine. 



The following graphical formula shows the constitution of 

 kairine : — 



C^HjCOH) < N(CH3)CH, 



A 



HCl 



Antipyrine, the second of these febrifuges, was discovered in 1883 

 by Dr. L. Knorr in Erlangen, and its physiological properties were 

 investigated by Prof. Filehne of Erlangen. The materials used in 

 the manufacture of antipyrine are aniline and aceto-acetic ether. The 

 aniline is first converted into phenylhydrazine, a body discovered by 

 Emil Fischer in 1876. This body combines directly with aceto-acetic 

 ether, with separation of water and alcohol, to form a body called 

 pyrazol (C10H10N2O). The methyl derivative of pyrazol derived by 

 treating it with iodide of methyl, is antipyrine, its composition being 

 C11H12N2O. As a febrifuge, antipyrine is superior in many respects 

 to kairine and even to quinine itself. It equals kairine in the certainty 

 of its action whilst in its duration it resembles quinine. It is almost 

 tasteless and odourless, is easily soluble in cold water, and takes the 

 form of a white crystalline powder. Its use as a medicine is accom- 



