Alteration of certain pharmacological effects of histamine by selected histaminase inhibitors
Angelakos, Evangelos Theodorou
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Compounds known to be histaminane inhibitors in vitro were studied for their ability to potentiate certain pharmacological effects of histamine. If histaminase plays a limiting role in the biological responses to histamine, histaminase inhibitors could serve as pharmacological tools in attempts to elucidate the problem of the possible physiological role of this naturally occurring and biologically highly active amine. The available information on histamine metabolism, histaminase (diamine oxidase), and histaminase inhibitors, was reviewed. The latter may be grouped into: 1) carbonyl reagents (semi-carbazides, hydroxylamines, hydrazines), and 2) substituted or unsubstituted diamines and guanidines. Recent evidence (Schayer et al. 1952, 1953) shows that aminoguanidine and other histaminase inhibitors block the major catabolic pathway of histamine in rats and, to a certain extent, in guinea pigs. Iproniazid (a hydrazine), a potent inhibitor of amine oxidase, blocks the main catabolic pathway of histamine in mice and cats. These two metabolic pathways for histamine catabolism are distinct and apparently related to different enzyme systems. In very recent reports, histaminase inhibitors are said to act as specific potentiators of histamine in the response of highly sensitive smooth muscle preparations (Arunlakshana et al. 1954; Lindel & Westling, 1954; D.J. Smith, 1953). The reported degree of potentiation is small, but it is not clear whether this is due to the same original high sensitivity of the tissue, wich may act as a limiting factor. The published results do not establish that the reported effect is related to inhibition of histaminase, since the possibility is not excluded that the compounds may act as sensitizers of histamine receptors on smooth muscle for which they appear to have some affinity (Ariens, 1954). [TRUNCATED]
Thesis (Ph.D.)--Boston University
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