Histamine 2- ethylamine

A survey of the BAs content in red and white Italian wines measured with the method proposed by Soleas and co-workers (1999) is reported in Table 4.3. Significant differences for histamine, ethylamine, thyra-mine, phenylethylamine, putrescine and cadaverine, were observed. 

ReceptorAg onists. In the histamine molecule there are two principal stmctural elements an imidazole moiety and an ethylamine side chain (16). Only the N -position is absolutely necessary for agonism. The imidazole ring can be replaced, eg, 2-pyridylethylamine,... 

The classical histamine receptor antagonists are stmcturaHy very similar, all being substituted ethylamines (2). Table 1 presents a member of each stmctural subclass. Presumably, the ethylamine core is needed to accomplish nonfmitfiil binding to the high affinity conformation of the receptor. 

Note The pre- and post-treatment of the chromatograms with the basic tri-ethylamine solution, which can be replaced by an alcoholic solution of sodium hydroxide [1,4] or a phosphate buffer solution pH = 8.0 (c = 0.2 mol/1) [5], serves to stabilize the fluorescence of the amino derivatives [2]. A final spraying with methanolic hydrochloric acid (chci = 5 mol/1) or 70% perchloric acid renders the detection reaction highly specific for histamine [4] and for catecholamines and indolamines [5]. 

FIGURE 5.19 Method of Barlow for measurement of affinity of a partial agonist, (a) Guinea pig ileal smooth muscle contraction to histamine (filled circles) and partial histamine receptor agonist E-2-P (N,N-diethyl-2-(l-pyridyl)ethylamine (open circles). Dotted lines show equiactive concentrations of each agonist used for the double reciprocal plot shown in panel b. (b) Double reciprocal plot of equiactive concentrations of histamine (ordinates) and E-2-P (abscissae). Linear plot has a slope of 55.47 and an intercept of 1.79 x 10s. This yields a KB (1 — tp/ta) = 30.9 pM. (c) Variant of double reciprocal plot according to Equation 5.8. (d) Variant of double reciprocal plot according to Equation 5.10. Data redrawn from [10],... 

Kenakin, T. P., and Cook, D. A. (1980). N,N-Diethyl-2-(l-pyridyl)ethylamine, a partial agonist for the histamine receptor in guinea pig ileum. Can. J. Physiol. Pharmacol. 58 1307-1310. 

The chemical structure of histamine has similarities to the structures of other biogenic amines, but important differences also exist. Chemically, histamine is 2-(4-imidazolyl)ethylamine (Fig. 14-1). The ethylamine backbone is a common feature of many of the amine transmitters (e.g. dopamine, norepinephrine and serotonin). However, the imidazole nucleus, absent from other known transmitters, endows histamine with several distinct chemical properties. Among these is prototypic tautomerism, a property that permits it to exist in two different chemical forms (Fig. 14-1). The tautomeric properties of histamine are thought to be critical in the... 

Histamine (2-[4-imidazole] ethylamine) is a low-molecular-weight amine synthesized from L-histidine exclusively by histidine decarboxylase. It is produced by various cells throughout the body, including central nervous system neurons, gastric mucosa parietal cells, mast cells, basophils and lymphocytes [1-4]. Since its discovery as a uterine... 

The most common Hj antihistamine drugs are structurally similar to histamine with a substituted ethylamine side chain however, they have two aromatic rings and can be formally represented by the general formula ... 

The Hi-receptor antagonists for the most part are substituted ethylamine compounds. In comparison with histamine, the Hi-antagonists contain no imidazole ring and have substituents on the side chain amino group. 

Synthesis. Histamine, 2-(4-imidazolyl)ethylamine, is formed by decarboxylation of histidine by the enzyme l.-histidinc decarhoxylase. Most histamine is stored preformed in cytoplasmic granules of mast cells and basophils. 

There is general consensus on the fact that the endogenous agonist histamine, 2-(imidazole-4-yl)ethylamine, binds to the receptor in its monocationic state (protonated at the side chain amine group). The monocationic form is predominantly (96.6%) present at pH 7.4 [11]. In this state, the neutral imidazole ring can exist in two different tautomeric forms, denominated by proximal (it) and tele (x), respectively (Figure 1). 

An interesting observation in our structure-activity studies was that ethylamine, a part of the histamine molecule, 4-(2-ethylamine)imidazole, known for a long time to be a potent stimulator of gastric secretion, also produced duodenal ulcers in rats (20,22). Furthermore, structural similarities also exist between dopamine and histamine H receptor antagonists metiamide and cimetidine (23,24). 

Fig. 6A.2 Means and 95% confidence intervals for histamine, tyramine, putrescine, methylamine, ethylamine, phenylethylamine and cadaveiine in the seven stages of the elaboration process (1) must (2) after AF (3) during MLF (4) just after MLF (5) after MLF and addition of SO2 (6) after 6 months of aging, (7) after 12 months of aging. Means with the same letter are not significantly different by the Fisher LSD test (from Marcobal et al. 2006a, with permission)...

Number of samples Histamine Methylamine Ethylamine Tyramine Phenylethylamine Putrescine Cadaverine... 

The early antihistamines. Hi histamine receptor antagonists, bore some structural resemblance to histamine and, like histamine, contained an ethylamine group. However, the structures of the many antihistamines that are available are disparate, and the traditional classification according to chemical structure (ethanolamine, ethy-lenediamine, alkylamine, piperazine, and phenothiazine) is outdated, since the second-generation antihistamines, such as terfenadine and astemizole, do not readily fit into the old classification system (2). 

Histamine, known trivially as 4(5-)(2-aminoethyl)imidaxole. structurally is composed of an imida/.ole heterocycle and ethylamine side chain. The methylene groups of the amino-ethyl side chain are designated a and p. The. side chain is attached, via the /S-CHa group, to the 4 position of an imida/.-ole ring. The imida/.ole N at position 3 is de.signatcd the pros 17T) N. whereas the N at position I i,s termed the tele (r) N. The side chain N is distinguished as N". 

The imidazol coordinates were taken from an x-ray diffraction crystallographic study of histamine (24) with a proton being substituted for the ethylamine side chain of histamine. The coordinates of other reactants, products, and intermediate complexes were calculated employing idealized hybridization and average bond distances or are as discussed. 

Potent agonists for the Hg receptor are obtained by simple modifications of the histamine molecule. The imidazole ring is very important for Hg agonistic activity [17]. Methylation of one of the nitrogens or replacements with other aromatic ring systems are not tolerated [22]. In contrast, subtle changes of the ethylamine side chain have proven to be very usefiil [17]. 

Fig. 13. Separation of amines including histamine and iV-dimethylhistainine as acetyl derivatives at 198°C with an F-60-Z phase /8HO-PE = jS-hydroxyphenyl-ethylamine ME-HIST = iV-dimethyUiistamine TYR = tyramine HIST = histamine 3-MeO-TYR = 3-methoxytyramine OCTOP = octopamine TRYPT = tryptamine MET = metanephrine NORMET = nonnetanephrine. Reproduced from Brooks and Homing (B24) with permission.

The important group of histamine is believed to be the ethylamine. The first antihistamine j... 

Such considerations do not, however, exclude the participation of the nonspecific enzyme as a source of body histamine. The non-specific histidine decarboxylase of guinea-pig kidney is known to have a high affinity for DOPA and 5-HTP, but a low affinity for histidine and phenylalanine . At first sight, then, it would appear that this enzyme is more likely to produce dopamine and 5-hydroxytryptamine than to form histamine or / -phenyl-ethylamine. It must be remembered, however, that the substrates DOPA and 5-HTP are not normally detectable in blood or tissues, while histidine and phenylalanine are present in amounts which compensate for the low affinity of the enzyme for these two amino acids. In terms of the capacity to form the corresponding amines, therefore, there is no reason to suppose that the decarboxylation of histidine is a less important function of the non-specific enzyme than is the decarboxylation of its other substrates. 

STRUCTURE-ACTIVITY RELATIONSHIP All the available Hj-receptor antagonists are reversible competitive inhibitors of the interaction of histamine with Hj receptors. Like histamine, many Hj antagonists contain a substituted ethylamine moiety. Unlike histamine, which has a primary amino group and a single aromatic ring, most Hj antagonists have a tertiary amino group linked by a two- or three-atom chain to two aromatic substituents (e.g., diphenhydramine). 

Histamine [2-(imidazol-4-yl)ethylamine] was synthesized and its effects in model biological systems were studied before it was found physiologically. Its synthesis occurs in many tissues, including mast cells, parietal cells of the gastric mucosa, and neurons of the central nervous system (CNS) and the periphery. Early hypotheses about its physiological function were based on the observed, dramatic effects of histamine in guinea pigs. These effects... 

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