Histamine substituted in any position with one or more methyl groups. Many of these are agonists for the H1, H2, or both histamine receptors.

Major changes in the brain histamine system of the ground squirrel Citellus lateralis during hibernation. (1/118)

Hibernation in mammals such as the rodent hibernator Citellus lateralis is a physiological state in which CNS activity is endogenously maintained at a very low, but functionally responsive, level. The neurotransmitter histamine is involved in the regulation of diurnal rhythms and body temperature in nonhibernators and, therefore, could likely play an important role in maintaining the hibernating state. In this study, we show that histamine neuronal systems undergo major changes during hibernation that are consistent with such a role. Immunohistochemical mapping of histaminergic fibers in the brains of hibernating and nonhibernating golden-mantled ground squirrels (C. lateralis) showed a clear increase in fiber density during the hibernating state. The tissue levels of histamine and its first metabolite tele-methylhistamine were also elevated throughout the brain of hibernating animals, suggesting an increase in histamine turnover during hibernation, which occurs without an increase in histidine decarboxylase mRNA expression. This hibernation-related apparent augmentation of histaminergic neurotransmission was particularly evident in the hypothalamus and hippocampus, areas of importance to the control of the hibernating state, in which tele-methylhistamine levels were increased more than threefold. These changes in the histamine neuronal system differ from those reported for the metabolic pattern in other monoaminergic systems during hibernation, which generally indicate a decrease in turnover. Our results suggest that the influence of histamine neuronal systems may be important in controlling CNS activity during hibernation.  (+info)

In vivo demonstration of H3-histaminergic inhibition of cardiac sympathetic stimulation by R-alpha-methyl-histamine and its prodrug BP 2.94 in the dog. (2/118)

1. The aim of this study was to investigate whether histamine H3-receptor agonists could inhibit the effects of cardiac sympathetic nerve stimulation in the dog. 2. Catecholamine release by the heart and the associated variation of haemodynamic parameters were measured after electrical stimulation of the right cardiac sympathetic nerves (1-4 Hz, 10 V, 10 ms) in the anaesthetized dog treated with R-alpha-methyl-histamine (R-HA) and its prodrug BP 2.94 (BP). 3. Cardiac sympathetic stimulation induced a noradrenaline release into the coronary sinus along with a tachycardia and an increase in left ventricular pressure and contractility without changes in mean arterial pressure. Intravenous administration of H3-receptor agonists significantly decreased noradrenaline release by the heart (R-HA at 2 micromol kg(-1) h(-1): +77 +/- 25 vs +405 +/- 82; BP 2.94 at 1 mg kg(-1): +12 +/- 11 vs +330 +/- 100 pg ml(-1) in control conditions, P < or = 0.05), and increases in heart rate (R-HA at 2 micromol kg(-1) h(-1): +26 +/- 8 vs +65 +/- 10 and BP 2.94 at 1 mg kg(-1): +30 +/- 8 vs 75 +/- 6 beats min(-1), in control conditions P < or = 0.05), left ventricular pressure, and contractility. Treatment with SC 359 (1 mg kg(-1)) a selective H3-antagonist, reversed the effects of H3-receptor agonists. Treatment with R-HA at 2 micromol kg(-1) h(-1) and BP 2.94 at 1 mg kg(-1) tended to decrease, while that with SC 359 significantly increased basal heart rate (from 111 +/- 3 to 130 +/- 5 beats min(-1), P < or = 0.001). 4. Functional H3-receptors are present on sympathetic nerve endings in the dog heart. Their stimulation by R-alpha-methyl-histamine or BP 2.94 can inhibit noradrenaline release by the heart and its associated haemodynamic effects.  (+info)

The histamine H3 receptor agonist N alpha-methylhistamine produced by Helicobacter pylori does not alter somatostatin release from cultured rabbit fundic D-cells. (3/118)

BACKGROUND: The mechanisms underlying the suppression of somatostatin dependent reflexes in Helicobacter pylori infection are not fully determined. The H pylori product N alpha-methylhistamine and inflammatory mediators such as tumour necrosis factor-alpha (TNF-alpha) may be responsible for the alterations in somatostatin release. AIMS: To examine the effect of N alpha-methylhistamine on somatostatin release from cultured somatostatin-secreting D-cells. METHODS: Rabbit fundic D-cells were obtained by collagenase-EDTA digestion and enriched by centrifugal elutriation and cultured for 40 hours. The effects of N alpha-methylhistamine on somatostatin release soon after stimulation (two hours) and after more prolonged exposure (24 hours) were assessed. RESULTS: N alpha-Methylhistamine (1 nM-1 microM) had no effect on basal or carbachol or adrenaline stimulated release over two hours. Similarly with prolonged exposure no effect on somatostatin cell content or release was identified. In contrast, TNF-alpha (24 hours) led to a dose dependent fall in both somatostatin content and release. CONCLUSIONS: N alpha-Methylhistamine had no direct inhibitory effects on D-cells, but TNF-alpha both significantly reduced the cellular content and inhibited release. Inflammatory cytokines, rather than N alpha-methylhistamine, are therefore likely to be responsible for directly inhibiting D-cell function in H pylori infection.  (+info)

Cloning and functional expression of the human histamine H3 receptor. (4/118)

Histamine regulates neurotransmitter release in the central and peripheral nervous systems through H3 presynaptic receptors. The existence of the histamine H3 receptor was demonstrated pharmacologically 15 years ago, yet despite intensive efforts, its molecular identity has remained elusive. As part of a directed effort to discover novel G protein-coupled receptors through homology searching of expressed sequence tag databases, we identified a partial clone (GPCR97) that had significant homology to biogenic amine receptors. The GPCR97 clone was used to probe a human thalamus library, which resulted in the isolation of a full-length clone encoding a putative G protein-coupled receptor. Homology analysis showed the highest similarity to M2 muscarinic acetylcholine receptors and overall low homology to all other biogenic amine receptors. Transfection of GPCR97 into a variety of cell lines conferred an ability to inhibit forskolin-stimulated cAMP formation in response to histamine, but not to acetylcholine or any other biogenic amine. Subsequent analysis revealed a pharmacological profile practically indistinguishable from that for the histamine H3 receptor. In situ hybridization in rat brain revealed high levels of mRNA in all neuronal systems (such as the cerebral cortex, the thalamus, and the caudate nucleus) previously associated with H3 receptor function. Its widespread and abundant neuronal expression in the brain highlights the significance of histamine as a general neurotransmitter modulator. The availability of the human H3 receptor cDNA should greatly aid in the development of chemical and biological reagents, allowing a greater appreciation of the role of histamine in brain function.  (+info)

Increased formation of thromboxane in vivo in humans with mastocytosis. (5/118)

Clinical manifestations of mastocytosis are mediated, at least in part, by release of the mast cell mediators histamine and prostaglandin D2. It has been previously reported that in addition to prostaglandin D2, mast cells produce other eicosanoids, including thromboxane. Nonetheless, little information exists regarding the formation of other prostanoids in vivo. The most accurate method to examine the systemic production of eicosanoids in vivo is the quantitation of urinary metabolites. We previously developed a highly accurate assay employing mass spectrometry to measure a major urinary metabolite of thromboxane, 11-dehydro-thromboxane B2, in humans. We utilized this assay to quantitate thromboxane production in 17 patients with histologically proven mastocytosis. We report that thromboxane formation was significantly increased (>2 SD above the mean) in at least one urine sample from 65% of patients studied. Of these, 91% of patients with documented systemic involvement had elevated thromboxane generation. In addition, endogenous formation of thromboxane was highly correlated with the urinary excretion of the major urinary metabolite of prostaglandin D2 (r = 0.98) and Ntau-methylhistamine (r = 0.91), suggesting that the cellular source of increased thromboxane in vivo could be the mastocyte. Enhanced thromboxane formation in patients with this disorder is unlikely to be of platelet origin as other markers of platelet activation, platelet factor 4 and beta-thromboglobulin, were not increased in three patients with marked overproduction of thromboxane. Furthermore, the recovery of 11-dehydro-thromboxane B2 excretion in two patients after the administration of aspirin occurred significantly more rapidly than the recovery of platelet thromboxane generation. These studies, therefore, report that thromboxane production is significantly increased in the majority of patients with mastocytosis that we examined and provide the basis to elucidate the role of this eicosanoid in disorders of mast cell activation.  (+info)

Differential effect of histamine 3 receptor-active agents on brain, but not peritoneal, mast cell activation. (6/118)

The activation of presynaptic histamine 3 (H(3)) receptors inhibits the release of histamine and other neurotransmitters from central nervous system neurons. Rat brain mast cells (MCs) release histamine and 5-hydroxytryptamine (5-HT) in response to neuropeptides and neurotransmitters secreted from adjacent neurons. Dura MCs also degranulate in response to antidromic trigeminal nerve stimulation and with acute psychological stress. Such findings have implicated brain MCs in certain neuroinflammatory disorders, such as migraines. We investigated the ultrastructural appearance of control and stimulated thalamic/hypothalamic (brain) MCs before and after treatment with the H(3) receptor agonist N(alpha)-methylhistamine (N(alpha)-mH) and the H(3) receptor antagonist thioperamide (Th). Ultrastructural investigation of brain MCs stimulated with compound 48/80 revealed extensive intragranular changes that paralleled 5-HT secretion but without degranulation by exocytosis typical of connective tissue MCs. N(alpha)-mH significantly reduced these morphological changes, as well as 5-HT release from brain MCs and neurons stimulated with KCl; conversely, Th augmented both histamine and 5-HT release from brain neurons and MCs. Neither N(alpha)-mH nor Th had any effect on peritoneal MCs. Simultaneous addition of both drugs largely antagonized each other's effects on brain MC activation and 5-HT secretion. Ultrastructural observations and lack of lactic dehydrogenase release in the perfusate excluded any cytotoxic effect. The ability of H(3) agonists to inhibit brain MC activation, as well as secretion of 5-HT from both brain MCs and neurons, may be useful in the management of migraines.  (+info)

Hypothalamic neuronal histamine as a target of leptin in feeding behavior. (7/118)

Leptin, an ob gene product, has been shown to suppress food intake by regulating hypothalamic neuromodulators. The present study was designed to examine the involvement of brain histamine in leptin-induced feeding suppression. A bolus infusion of 1.0 microg leptin into the rat third cerebroventricle (i3vt) elevated the turnover rate of hypothalamic neuronal histamine (P < 0.05) as assessed by pargyline-induced accumulation of tele-methylhistamine (t-MH), a major metabolite of histamine. No remarkable change in the mRNA expression of histidine decarboxylase (HDC), a histamine-synthesizing enzyme, was observed in the hypothalamus after i3vt infusion of leptin. These results indicate that leptin increases histamine turnover by affecting the posttranscriptional process of HDC formation or histamine release per se. As expected, concomitant suppression in 24-h cumulative food intake was also observed after infusion of leptin. Systemic depletion of brain histamine levels by pretreatment with an intraperitoneal injection of 224 micromol/kg alpha-fluoromethylhistidine (FMH), a suicide inhibitor of HDC, attenuated the leptin-induced feeding suppression by 50.7% (P < 0.05). This attenuation of feeding suppression was mimicked by the i3vt infusion of 2.24 micromol/kg FMH before leptin treatment (P < 0.05). In addition, concentrations of hypothalamic histamine and t-MH were lowered in diabetic (db/db) mice, which are known to be deficient in leptin receptors (P < 0.05 vs. lean littermates for each amine), although the amine levels were higher in diet-induced obese rats (P < 0.05 for each amine). Leptin-deficient obese mice (ob/ob) showed lower histamine turnover (P < 0.05 vs. lean littermates), which recovered after leptin infusion. Thus, a growing body of results points to an important role for the hypothalamic histamine neurons in the central regulation of feeding behavior controlled by leptin.  (+info)

Histamine H(3)-receptor antagonists inhibit gastroprotection by (R)-alpha-methylhistamine in the rat. (8/118)

(R)-alpha-methylhistamine, a selective agonist of histamine H(3) receptors, is capable of protecting the gastric mucosa against differently acting damaging agents. The objective of the present study was to determine whether H(3) receptors mediate its protective action in the rat. Gastric mucosal lesions were induced intragastrically (i.g.) by 0.6 N HCl, 1 ml rat(-1). (R)-alpha-methylhistamine, 100 mg kg(-1) i.g., substantially reduced the severity of macroscopically and histologically assessed damage caused by concentrated acid. Prior treatment with highly selective H(3)-receptor antagonists, ciproxifan (0.3, 1 and 3 mg kg(-1) i.g.) and clobenpropit (3, 10 and 30 mg kg(-1) i.g.), dose-dependently inhibited the protection exerted by (R)-alpha-methylhistamine up to a complete reversal. When given alone at high doses, both antagonists tended to worsen the HCl-induced histologic damage. During basal conditions, (R)-alpha-methylhistamine, 100 mg kg(-1) i. g., caused a significant increase in titratable acidity of the gastric juice. Prior treatment with ciproxifan (3 mg kg(-1) i.g.) and clobenpropit (30 mg kg(-1) i.g.) did not alter the secretory response to (R)-alpha-methylhistamine. Clobenpropit alone, but not ciproxifan, increased the volume of gastric juice, and both compounds alone had no effect on titratable acid. Present findings support evidence that H(3) receptors are actively involved in the maintenance of gastric mucosal integrity, with no apparent role in the regulation of basal gastric acid secretion.  (+info)

Methylhistamines are not a recognized medical term or a specific medical condition. However, the term "methylhistamine" may refer to the metabolic breakdown product of the antihistamine drug, diphenhydramine, which is also known as N-methyldiphenhydramine or dimenhydrinate.

Diphenhydramine is a first-generation antihistamine that works by blocking the action of histamine, a chemical released during an allergic reaction. When diphenhydramine is metabolized in the body, it is converted into several breakdown products, including methylhistamines.

Methylhistamines are not known to have any specific pharmacological activity or clinical significance. However, they can be used as a marker for the presence of diphenhydramine or its metabolism in the body.

3. Methylhistamines". Journal of Medicinal Chemistry. 19 (7): 923. doi:10.1021/jm00229a013. PMID 7675. Durant, G. J.; Emmett, J ...
... methylhistamines MeSH D03.383.129.308.385 - histidinol MeSH D03.383.129.308.411 - hydantoins MeSH D03.383.129.308.411.105 - ...
... methylhistamines MeSH D02.092.211.215.581 - 2-hydroxyphenethylamine MeSH D02.092.211.215.801 - tryptamines MeSH D02.092.211.215 ... methylhistamines MeSH D02.092.471.562 - mercaptoethylamines MeSH D02.092.471.562.369 - cysteamine MeSH D02.092.471.600 - ...
3. Methylhistamines". Journal of Medicinal Chemistry. 19 (7): 923. doi:10.1021/jm00229a013. PMID 7675. Durant, G. J.; Emmett, J ...
Nizamutdinova IT, Dusio GF, Gasheva OY, Skoog H, Tobin R, Peddaboina C, Meininger CJ, Zawieja DC, Newell-Rogers MK, Gashev AA. Mast cells and histamine are triggering the NF-?B-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation. Aging (Albany NY). 2016 11 21; 8(11):3065-3090 ...
Methylhistamines Preferred Term Term UI T026110. Date01/01/1999. LexicalTag NON. ThesaurusID NLM (1977). ... Methylhistamines Preferred Concept UI. M0013643. Registry Number. 0. Scope Note. Histamine substituted in any position with one ... Methylhistamines. Tree Number(s). D02.092.211.215.501.621. D02.092.471.440.500. D03.383.129.308.373.500. Unique ID. D008761. ...
Methylhistamines Preferred Term Term UI T026110. Date01/01/1999. LexicalTag NON. ThesaurusID NLM (1977). ... Methylhistamines Preferred Concept UI. M0013643. Registry Number. 0. Scope Note. Histamine substituted in any position with one ... Methylhistamines. Tree Number(s). D02.092.211.215.501.621. D02.092.471.440.500. D03.383.129.308.373.500. Unique ID. D008761. ...
Methylhistamines - Preferred Concept UI. M0013643. Scope note. Histamine substituted in any position with one or more methyl ...
PMID- 5098082 TI - Methyl histamines and gastric secretion. AB - 1. The previous findings that N-methylhistamine and N- ...
N0000168434 Methylglucosides N0000168419 Methylglycosides N0000166584 Methylguanidine N0000167070 Methylhistamines N0000170244 ...
D8.811.682.662.290 Methylhistamines D3.383.374.373.500 D3.383.129.308.373.500 Methylthioinosine D2.886.759.800.500 Metipranolol ...

No FAQ available that match "methylhistamines"