Histamine formation was measured by the [14C]histamine content of the stomach following injection of [14C]histidine into rats. Carbonyl reagents (e.g. oxyamines) which inactivate pyridoxal phosphate, the co-enzyme of histidine decarboxylase, were the most effective inhibitors of histamine formation in vivo. Although the oximes prepared from imidazol-4(5)-ylmethoxyamine and pyridoxal or pyridoxal phosphate cannot inactivate the co-enzyme, they proved sufficiently potent to merit further study as inhibitors of histamine formation in vivo.Many compounds of diverse chemical structure are active in vitro as histidine decarboxylase inhibitors. Of these only a few, mainly carbonyl reagents such as oxyamines and hydrazine derivatives which inactivate the co-enzyme pyridoxal phosphate (PLP), have been shown to inhibit histamine formation in vivo (Levine, Sat0 & Sjoerdsma, 1965;Johnston & Kahlson, 1967;Reilly & Schayer, 1968;Hakanson & Liedberg, 1972;Kobayashi, Kupelian & Maudsley, 1970;Menon, Clark & Aures, 1971). Carbonyl reagents are generally extremely potent inhibitors of histidine decarboxylase, but because of their action on the co-enzyme they lack specificity and may thus also inhibit other PLP-dependent enzymes.A procedure for the screening of potential inhibitors of histidine decarboxylase in vivo is now described and applied to the evaluation of compounds selected from those previously studied in vitro (Mole & Shepherd, 1972). MATERIALS A N D METHODS DrugsWe Oxime (PLPZMA) of pyridoxal phosphate and imidazol-4(5)-ylmethoxyamineImidazol-4(5)-ylmethoxyamine dihydrochloride (IMA) (Mole & Shepherd, 1972) (1.86 g, 0.01 mol) was dissolved in 50 ml water and added to solid pyridoxal phosphate monohydrate (2.658, 0.01 mol). The mixture was stirred until a clear solution was obtained (about 30 min) and set aside at 4" for 2 h. Sodium bicarbonate (1*68g, 0.02 mol) in 50 ml water was added during 30 min to the stirred solution which was then left overnight at 4". The yellow solid which separated was removed by filtration and washed carefully with ice-cold water to give 2.80g (78 %) of oxime, mp 178-183".
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.