ANALOGS OF PYRIDOXAL 573 



since it is not of renal origin and hence due to an increased urea formation. 

 Administration of 100 //g/rat/day of deoxypyridoxol for 28 days apparently 

 increases urea formation in liver slices in both deficient and pyridoxine-fed 

 animals (see accompanying tabulation), although the authors stated that 



deoxypyridoxol lessens the deficiency abnormalities rather than accentuat- 

 ing them (Beaton et al., 1954). The cycle of urea formation does not require 

 pyridoxal directly, but the aspartate to condense with citrulline must be 

 formed by transamination reactions, so that one might expect impaired 

 pyridoxal function to depress urea formation by this mechanism, and per- 

 haps it counteracts to some extent the efl"ect of an increased supply of amino 

 acids for catabolism. 



Convulsive seizures in mice are produced by the injection of 4-methoxy- 

 methylpyridoxol, and are completely prevented by pyridoxol in a dose 3 

 times that of the analog (Gammon et al., 1960). The convulsions can also 

 be prevented by prior administration of y-aminobutyrate but not by any 

 of the other related amino acids or products of glutamate metabolism test- 

 ed. Since glutamate decarboxylase requires pyridoxal-P, the most obvious 

 explanation would be that the analog reduces brain y-aminobutyrate, there- 

 by initiating convulsions, and that the administration of y-aminobutyrate 

 simply restores the normal level or prevents depletion. Others have suggest- 

 ed that certain carbonyl reagents, such as thiosemicarbazide, produce sei- 

 zures by reducing brain y-aminobutyrate, and many now believe that ceU' 

 tral motor activity is controlled bj^ the levels of such amino acids and their 

 corresponding amines. Analyses of mouse brains obtained during convul-' 

 sions from 4-methoxymethylpyridoxol and other analeptics were thus made, 

 and it was found that y-aminobutyrate drops 50-70% when the analog is 

 used but shows no significant change when the convulsions are due to Me- 

 trazol, picrotoxin, or electroshock (Gammon et al., 1960; Kamrin and Kam- 

 rin, 1961). Despite the coherence of these observations in supporting the 

 role of y-aminobutyrate in antipyridoxine convulsions, one additional fact 

 is difficult to fit in: the administration of pyridoxol, which blocks the sei- 

 zures, does not alter the fall in brain y-aminobutyrate. It has also been 

 shown that administration of y-aminobutyrate to animals with seizures pro- 

 duced by the analog does not reduce the seizures although the y-amino- 



