ANALOGUES 



hexahydronicotinic acid, inhibited the fermentative activity of 

 apozymase and cozymase.^® 



Pyridine-j8-sulphonic acid did not produce symptoms of nicotinic 

 acid deficiency when fed to mice.^* 



Sulphapyridine, in common with many other sulphonamides, has 

 a bacteriostatic action on S. aureus, but part of this is believed to be 

 due to an antagonistic effect on nicotinic acid, although the addition 

 of nicotinic acid did not counteract the effect ^^ as it did with pyridine- 

 ^-sulphonic acid. Sulphapyridine inhibited the response of nicotinic 

 acid-deficient dogs to nicotinamide.^^ Sulphapyridine, like pyridine- 

 ^-sulphonic acid, had an affinity for apodehydrogenase and was able 

 to displace cozymase and inhibit dehydrogenation.^^ 



Another substance antagonistic to nicotinic acid is 3-acetyl-pyri- 

 dine, which produced symptoms of nicotinic acid deficiency when 

 fed at a level of 2 mg. or more per day to mice maintained on a purified 

 diet ; the effect was abolished by administration of nicotinic acid ^^ 

 or tryptophan. 3 8 3- Acetyl-pyridine had only a slight inhibitory effect 

 on the growth of bacteria, and this was not reversed by nicotinic acid.^^ 

 Sjyw. -dinicotinylhydrazine did not antagonise nicotinic acid.^^ 



2- and 6-Fluoronicotinic acid *^ and 5-fluoronicotinic acid and its 

 amide ^^ have been prepared. The first two compounds did not 

 inhibit the growth of E. coli, S. aureus or 5. viridans, in vitro at a 

 dilution of i in 2000. 6-Aminonicotinic acid, on the other hand, 

 inhibited the growth of S. aureus at a dilution of i in 10^, and the 

 inhibition was reversed by nicotinic acid or amide. ^^ 



Comparison of Activities of Nicotinic Acid Analogues on Diflferent 

 Species of Organisms 



A comprehensive survey of the biological activity of various com- 

 pounds related to nicotinic acid was made by Ellinger et al.^^ All the 

 compounds tested had an action on the central nervous system. In 

 some, the exciting action predominated, as in nicotinic acid and 

 nicotinamide (see page 273), but many compounds were predomin- 

 antly narcotic, death resulting from paralysis of the respiratory centre. 

 All the compounds tested, with the exception of trigonelline, were con- 

 siderably more toxic than nicotinic acid or even the amide. All 

 the compounds which, it is generally agreed, possess anti-blacktongue 

 activity, namely nicotinic acid and its esters, nicotinamide and nico- 

 tinuric acid were converted into N^-methylnicotinamide by incubation 

 with liver or kidney slices. Many alkylated derivatives of nicotin- 

 amide and also ^-picoline were similarly converted to N^-methylnico- 

 t in amide. 



Rats can utilise, besides nicotinic acid and nicotinamide, the alkyl 



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