As already stated, both series occur in coal-tar and the pyridine series also more abundantly in bone-oil.  Pyridine, picoline, lutidine, and collidine, the first four members of the pyridine series, have, moreover, all been formed synthetically, although the processes are not such as would yield the products as cheaply as they can be gotten from Dippel’s oil.  Quinoline, the first member of the higher series, had been made synthetically by several chemists, but by expensive and involved methods, when Skraup, in 1881, effected its synthesis from nitrobenzol and glycerin, or still better, a mixture of nitrobenzol and aniline with glycerin.  This process allows of its being made on a commercial scale if desirable.  Shortly after, by an application of the same principle, Dobner and Miller effected the synthesis of lepidine, the second member of the quinoline series.

At the same time that this general agreement to consider these bases as the starting point in the endeavor to effect the synthesis of the natural alkaloids had been arrived at by chemists, it was thought well to look into the question whether these bases and their immediate derivatives had any therapeutic value of their own.

Piperidine, the decomposition product of piperine, which we have shown may be considered to be hexahydropyridine, was examined by Dr. Kronecker, of Berlin, at the request of Prof.  Hofmann, and was found to have an action upon animals in many respects resembling that of conine.  Prof.  Filehne, of Erlangen, who has studied a large number of these pyridine and quinoline derivatives, found, moreover, that the hydrochlorate of ethyl-piperidine had a physiological action quite analogous to that of conine.

The physiological action of quinoline itself has been studied quite extensively by Donath and others, and it was found that several of its salts were quite valuable febrifuges, acting very like quinine, and capable in cases of being used as a substitute for it.  In general, the hydrogen addition products were found to be more active than the simple base, an observation entirely in accord with the theory formed by Wischnegradsky, and by Konigs, as the result of the study of the decomposition products of the alkaloids, viz., the alkaloids are in general hydrogen addition products of pyridine and quinoline, or of the two bases combined.  Thus Prof.  Filehne found that hydrochlorate of tetrahydroquinoline was much more energetic in its action than quinoline, but could not be used on account of a too powerful local effect.  The hydrochlorate of dimethyl-tetrahydroquinoline, which was distinguished by its strong bitter taste, much resembling that of quinine, had an effect like that of curare poison.  The most decided febrifuge action, however was found by Prof.  Filehne to reside in the hydrochlorate of oxyhydro-methyl-quinoline, introduced to public notice by Prof.  O. Fischer under the name of “Kairin,” and in the acid sulphate of tetrahydro-methylquinoline, introduced under the name of “Kairolin.”  These compounds had a very surprising febrifuge action, without any unpleasant after effects or local disturbances.