NICOTINIC ACID (NIACIN) 



Nicotinamide 



Nicotinamide is a white substance crystallising from benzene in 

 needles, m.p. 131° C. It is very soluble in water (i in i) and in 95 % 

 alcohol (i in 1-5), soluble in glycerol (i in 10), but only slightly soluble 

 in ether. On distillation with phosphorus pentoxide it yields 3-cyano- 

 pyridine and on hydrolysis with acid or alkali it yields nicotinic acid. 

 On heating in a dry tube, pyridine is evolved. 



Nicotinamide sold in Great Britain for pharmaceutical purposes 

 must conform to certain standards laid down in the Sixth Addendum 

 of the British Pharmacopoeia, 1932, and modified in the 1948 edition. 

 Nicotinamide tablets were included in the Seventh Addendum. The 

 therapeutic dose is the same as for the acid, and the substance is 

 normally dispensed in 50-mg. tablets. 



Several N-alkyl derivatives of nicotinamide are known, of which 

 N-diethyl-nicotinamide is the well-known heart stimulant, Nikethamide 

 (Coramine). 



5. ESTI2VIATION OF NICOTINIC ACID 



It will already be evident from what has been said in the introduc- 

 tion that there is no satisfactory biological method of assaying the 

 pellagra-preventative factor. Rats and chickens fail to respond 

 specifically, whilst the prevention of blacktongue in dogs, although 

 specific, does not constitute a convenient method of assay. 



In spite of this, dogs were used for assaying foodstuffs by Waisman 

 et at.} whilst Schaefer et al.^ described a diet consisting of casein and 

 sucrose supplemented by aneurine, riboflavine, pantothenic acid and 

 choline, which was said to produce an uncomplicated nicotinic acid 

 deficiency in dogs, suitable for assay purposes. 



Fortunately, nicotinic acid and nicotinamide can readily be esti- 

 mated chemically or microbiologically, and the absence of a satisfac- 

 tory biological method of assay is not a serious disadvantage. 



Chemical Methods based on the Vongerichten Reaction 



One of the first chemical tests proposed was a modification of 

 Vongerichten 's reaction for pyridine compounds.^ P. Karrer and 

 H. Keller * used the reaction to estimate the amount of nicotinic acid 

 and nicotinamide in animal tissues. These were digested with water, 

 the aqueous extract was neutralised with potassium hydroxide solution 

 to liberate the nicotinic acid, the resulting solution was evaporated to 

 dryness and the residue extracted with benzene. The extract was 



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