Methyl histamines

Agonist 2-methyl-histamine Dimaprit R-(a )-methylhistamine 4-methylhistamine... 

Histamine occurs in the brain, particularly in certain hypothalamic neurons, and evidence is strong that histamine is a neurotransmitter. Distribution of histamine, its synthetic enzyme (histidine decarboxylase), and methyl histamine (the major brain metabolite) is not uniform. Possible roles for histamine in the regulation of food and water intake, thermoregulation, hormone release, and sleep have been suggested. Additional information on histamine can be found in Chapter 38. 

Beales, I.L.P., Calam, J., 1997. Effect of N -methyl-histamine on acid secretion in isolated cultured rabbit parietal cells implications for helicobacter pylori associated gastritis and gastric physiology. Gut 40, 14-19. 

H3 Receptor Agonist Activity of Imidazole-methylated Histamine Derivatives... 

In accordance with the pharmacological results above, introduction of an additional methyl in the -position of the side chain as well as in the A -position of the imidazole drastically decreases the H3 receptor agonist potency of (/ )-a-methyl-histamine (12). In particular, (/ -a.A -dimethylhistamine (15) displays a pD2 value of 5.8 [19] and (f )-a,A -dimethylhistamine (16) a value of 4.3 [20],... 

Due to its high selectivity and potency at H3 receptors (/ )-a-methylhistamine (12) is nowadays used as the standard agonist in pharmacological assays related to this receptor. With regard to its pharmacodynamic properties, which were substantiated in preclinical studies [40], (R)-a-methylhistamine (12) meets all criteria of a potential drug substance. However, in contrast to its pharmacodynamic potential (ft)-a-methyl-histamine (12) suffers from its pharmacokinetic drawbacks which limit its use in both pharmacological and conceivable clinical studies. 

As the pharmacokinetic properties of the azomethine prodrugs of (7 )-a-methyl-histamine (12) were found to strikingly depend on their physico-chemical properties, it was attempted to quantify the relationship between lipophilicity and CNS penetration of the benzophenone derived imines [50], The main obstacle to the experimental measurement of the azomethines log P values was the competing hydrolysis of the... 

Zinc and other metal ions have been found to promote pyrrole hydrogen ionization in 2-(2 -pyridyl)imidazole.269 Complexation studies114 on the systems N-methyl-histamine and NN-dimethylhistamine with bivalent zinc, copper, cobalt, and nickel have shown that the stabilities of the complexes follow the Irving-Williams series. With respect to the variation of a ligand with the same metal ion, the stability decreases in the series histamine, N-methylhistamine, NN-dimethylhistamine, possibly as a result of steric hindrance. The complexes are assigned the structure (12). 

From Leptodactylus pentadactylus, in addition to spinaceamine and 6-methylspinaceamine, the histidine-related bases histamine, -methyl-histamine, and yv ,A/ -dimethylhistamine (22) were also isolated (Section... 

In the mass spectra of a number of methylated histamine derivatives the base ions arise from /3-cleavage, usually with concomitant hydrogen rearrangement. This results in ions of the general form [M - CHR=NR] , where R = Me, H. 

Navert, H., New approach to the separation and identification of some methylated histamine derivatives by gas chromatography, J. Chromatogr., 106, 218-224, 1975. 

Histamine was found to be a neurotransmitter in the brain in 1982, by T. Watanabe from Tohoku University and H. Wada from Osaka University. It was associated with a presynaptic receptor, with methyl histamine acting as an agonist, and thioperamide as an antagonist. The histaminergic neuronal system has the same distribution in the body as the noradrenergic and serotonergic systems, and it is involved in memory, emotions, and behavior. No disease has yet been found to be due to a disturbance of the histaminergic neuronal system. 

In this paper, we have calculated the theoretical PA s relative to the ammonia, in the gas phase, of the following compounds histamine (4(5)-2 -aminoethylimidazole) (1), 2-methyl-histamine (2), 2-amino-histamine (3), 4-methyl-histamine (4), 4-chloro-hista-mine (5), 4-nitro-histamine (6), Na-methyl-histamine (7), N ,Na-dimethyl-histamine... 

Cohen and co-workers have reported a facile synthesis of 2-(trifluoro-methyl)histamine and 2-(trifluoromethyl)-L-histidine using histamine and L-histidine as starting materials, repectively. The desire to use histamine and histidine was mainly due to ready availability, which would lead to rapid synthetic sequences and a direct entry into the fluorinated L-amino acid series. cw-l,2-Dibenzamido-l-alkenes (34) prepared by the Bamberger imidazole cleavage of corresponding imidazoles (33) were condensed with trifluoroacetic anhydride at reflux (40 °C) to yield 2-trifluoromethyl substituted imidazoles (35) in about 70% yield. 

Methylhistamine, Fram and Green [47] have detected methyl-histamine as histamine metabolite in normal urine. The dinitrophenyl-methylhistamine was separated by TLC on a silica gel G layer and photometrically determined at 358 nm after elution. 

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