DIAMINE OXIDASE (HISTAMINASE) 



363 



guanidine was demonstrated by Schayer et al., (1954) by injecting labeled 

 cadaverine into mice and determining the C^^Og respired (Fig. 2-7). It is 

 much more effective than isoniazid or agmatine. The metabolism of hista- 

 mine should also be blocked by aminoguanidine. This was shown in three 

 psychiatric patients by administering labeled histamine and finding that 



100 



-1.5 -0.5 



LOG INH DOSE (^g/G) 



+ 0.5 



+ 1.5 



+ 2.5 



+ 3.5 



Fig. 2-7. Effects of diamine oxidase inhibitors on the oxidation of cadaverine in 

 mice, as determined by the formation of C'^Oj from labeled cadaverine. (Data from 



Schayer et al., 1954.) 



urinary imidazoleacetate-C^^ is reduced by aminoguanidine at 0.1-1 mg/kg 

 (Lindell et al., 1960). A larger fraction of the histamine is excreted as 

 methylhistamine, demonstrating a diversion of metabolic pathways by 

 this inhibitor. 



Diamine oxidase is not strongly inhibited by monoamidines, but diami- 

 dines, diguanidines, and diisothioureas of the proper chain lengths are 

 quite potent inhibitors (Blaschko et al., 1951). The data for these series 

 are summarized in Fig. 2-8. The correlation between chain length and 

 inhibition is not nearly so clear as for monoamine oxidase (Blaschko and 

 Duthie, 1945; Blaschko and Himms, 1955), and in some cases, as the dia- 

 midines, there is surprisingly little variation of inhibition with chain length. 

 For diamidines of n = 10-16, one wonders if the binding is actually to 



