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Inhibition Of Histamine Synthesis In The Rat By Alpha-Hydrazino Analog Of Histidine And 4-Bromo-3-Hydroxy Benzyloxyamine

, : Inhibition Of Histamine Synthesis In The Rat By Alpha-Hydrazino Analog Of Histidine And 4-Bromo-3-Hydroxy Benzyloxyamine. Biochemical Pharmacology 14: 139-149

Inhibitors of either specific or nonspecific histidine decarboxylase, or both, were studied in vitro and in vivo. Alpha-hydrazine analog of histidine (aHH) and 4-bromo-3-hydroxy benzyloxyamine (NSD-1055) were potent inhibitors of the specific enzyme, while a -methyldopa and a -methyldopa-hydrazine had little activity. The latter 2 compounds and NSD-1055 were potent inhibitors of the nonspecific decarboxylase. Only aHH and NSD-1055 altered histamine levels in vivo. Administration of these compounds to female rats resulted in decreased levels of histamine in heart (30%), stomach (50%), and urine (45%) but did not alter histamine levels in peritoneal mast cells. Animals whose tissue histamine levels were partially depleted by pretreatment with compound 48/80 showed little or no further lowering on administration of the histidine decarboxylase inhibitors. Administration of NSD-1055 to germ-free animals produced effects on tissue histamine similar to those in normal animals and decreased already low urinary histamine levels even further. The data suggest that histamine exists in rat tissues in at least 3 metabolic pools and that its synthesis in vivo is catalyzed primarily by the specific decarboxylase. Because of an apparent lack of toxicity, aHH should be a valuable research tool and warrants study as a potential therapeutic agent.


PMID: 14332459

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