ANALOGUES 



anilide were tested on dogs and found to possess considerable activity. 

 Several esters of nicotinic acid also exhibited biological activity when 

 tested on chicks ; ^^ the activity varied with the nature of the esterify- 

 ing group. Ethyl, propyl and butyl nicotinates were as effective as 

 the free acid in curing blacktongue in dogs and a similar condition in 

 chicks ; ^* their behaviour closely simulated that of a substance isolated 

 from wheat bran.^^ 



Esters of glycerol and two simple sugars were also found to cure 

 blacktongue in dogs.^^" When incorporated in rice they were not 

 removed on subsequent cooking. 



Activity in Pellagra 



Fewer discrepancies have been reported in the activities of nicotinic 

 acid derivatives in pellagra than in blacktongue, although in some 

 instances there is a marked difference in the behaviour of a particular 

 substance in the two conditions, sufficiently striking, in fact, to suggest 

 that whilst the conditions are analogous they are possibly due to a 

 breakdown of carbohydrate metabolism at two different points. Thus, 

 whereas quinolinic acid was found by four different groups of workers 

 to be inactive in blacktongue, R. W. Vilter and T. D. Spies ^® found 

 that it produced a dramatic response in pellagrins, and confirmed the 

 subjective improvement by demonstrating that the coenzyme I and 

 II content of the blood also increased to normal within twenty-four 

 hours. T. D. Spies and his colleagues ^^ found that, in addition to 

 nicotinic acid and the amide, nicotinethyl- and -diethylamide and ethyl 

 nicotinate were active in pellagra, whilst a-picoline, trigonelline and 

 2-aminopyridine were inactive. Results were inconclusive with 

 ;8-picoline, 2 : 6-dimethylpyridine-3 : 5-dicarboxylic acid and pyridine- 

 3 : 5-dicarboxylic acid. Similarly, pyrazine-mono- and di-carboxylic 

 acids, which according to two groups of workers were inactive in 

 blacktongue, were found to cause prompt disappearance of glossitis 

 in pellagrins, ^^' ^® whilst pyrazine-monocarboxylic acid increased the 

 coenzyme I content of erythrocytes and muscle to the same extent as 

 did nicotinic acid.^^ According to T. D. Spies and his colleagues ^^' ^^ 

 it also increased the amount of " factor V " (page 229), but this last 

 observation was at variance with the results of W. J. Dann et al.}^ 

 who found, using Haemophilus parainfluenzae to estimate the activity, 

 that neither pyrazine-monocarboxylic acid nor quinolinic acid could 

 effect an in vivo or in vitro synthesis of factor V in human blood. 



According to Axelrod et al.,^^ however, " the antipellagric value of 



a compound is not necessarily associated with its ability to affect the 



coenzyme I content of tissues " since they found " definite clinical 



improvement " in pellagrins treated with pyrazine-monocarboxylic 



19 289 



