290 PYRIDOXINE AND RELATED COMPOUNDS 



activity (Fig. 2) with accompanying clinical seizures was well established when 100 

 mg. of pyridoxine-HCl was given intramuscularly. For about 1 minute following 

 injection, there was little change in the EEG. However, by 3 minutes, activity had 

 definitely diminished and by 4-5 minutes after injection, the EEG became a normal 

 sleep record (Fig. 3). Clinically, the infant was of good color without added oxygen, 

 sleeping peacefully and showing no evidence of tremor or rigidity. In 48 hours, al- 

 though kept on the original formula, there was no evidence of previous difficulties." 



It is of interest that, as in animals, young infants appear to he more sus- 

 ceptible to convulsive seizures as manifestations of vitamin Be deficiency 

 than older children or adults. The critical level of vitamin Be intake lies 

 between 50 and 80 y per day. 



The biochemical defect characterizing the convulsive disorder in vita- 

 min Be deficiency has not yet been elucidated. 



Isoniazid may also produce grand mal convulsions in man which are 

 counteracted by pyridoxine, although perhaps not as completely as the 

 convulsive seizures occurring in simple, direct vitamin Be deficiency.^o^ 



XI. Pharmacology 



KLAUS R. UNNA 



Pyridoxine has an extremely lo>v toxicity. Doses up to 1 g. per kilogram 

 are tolerated without ill effects by rats, rabbits, and dogs.^ The metabolism, 

 the circulatory and respiratory systems, and isolated smooth muscle organs 

 of normal animals are not influenced by the vitamin. ^ Pyridoxine has been 

 reported to increase the contraction height and work output of perfused 

 frog muscles.- This effect was obtained only with concentrations between 

 0.00005 and 0.005 millimole per liter; a similar effect was obser\-ed b}^ the 

 same authors with thiamine and pantothenic acid in ( omparable concen- 

 trations. 



Little is known about the toxic effects of pyridoxal and pyridoxamine. 

 On injection of graded amounts of the different forms of the vitamin into 

 eggs, 5 mg. of pyridoxal reduced the hatchability more markedly than 5 

 mg. of pja'idoxine, whereas pyridoxamine was without effect in closes of 10 

 nig.3 Pyridoxamine in doses of 320 mg. per kilogram injected intraperi- 

 toneally in mice failed to cause toxic effects.* 



202 R. H. Reilly, K. F. Killam, E. H. Jenney, W. H. Marshall, T. Tausig, N. S. 

 Apter, and C. C. Pfeiffer, J. Am. Med. Assoc. 152, 1317 (1053). 



1 K. Unna, J. Pharmacol. Exptl. Therap. 70, 1 (1940). 



2 N. W. Shock and W. H. Sebrell, Jr., Am. J. Pht/siol. 146, 399 (1946). 



3 W. W. Cravens and E. 15. Snell, Proc. Sac. Exptl. Biol. Med. 71, 73 (1949). 



^ R. E. Parks, Jr., G. W. Kidder, and V. C. Dewey, Proc. Soc. Exptl. Biol. Med. 79, 

 287 (1952). 



