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H3 Receptor Antagonists (h3 + receptor_antagonist)

Distribution by Scientific Domains
Medical Sciences50%
Chemistry33%

Kinds of H3 Receptor Antagonists

  • histamine h3 receptor antagonist
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    Selected Abstracts

    Search for Histamine H3 Receptor Antagonists with Combined Inhibitory Potency at N, -Methyltransferase: Ether Derivatives.

    CHEMINFORM, Issue 22 2005
    J. Apelt
    Abstract For Abstract see ChemInform Abstract in Full Text. [source]

    Effects of a Novel Cognition-Enhancing Agent on Fetal Ethanol-Induced Learning Deficits

    ALCOHOLISM, Issue 10 2010
    Daniel D. Savage
    Background:, Drinking during pregnancy has been associated with learning disabilities in affected offspring. At present, there are no clinically effective pharmacotherapeutic interventions for these learning deficits. Here, we examined the effects of ABT-239, a histamine H3 receptor antagonist, on fetal ethanol-induced fear conditioning and spatial memory deficits. Methods and Results:, Long-Evans rat dams stably consumed a mean of 2.82 g ethanol/kg during a 4-hour period each day during pregnancy. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, litter size and birth weights were not different between the ethanol-consuming and control groups. Female adult offspring from the control and fetal alcohol-exposed (FAE) groups received saline or 1 mg ABT-239/kg 30 minutes prior to fear conditioning training. Three days later, freezing time to the context was significantly reduced in saline-treated FAE rats compared to control. Freezing time in ABT-239-treated FAE rats was not different than that in controls. In the spatial navigation study, adult male offspring received a single injection of saline or ABT-239 30 minutes prior to 12 training trials on a fixed platform version of the Morris Water Task. All rats reached the same performance asymptote on Trials 9 to 12 on Day 1. However, 4 days later, first-trial retention of platform location was significantly worse in the saline-treated FAE rats compared control offspring. Retention by ABT-239-treated FAE rats was similar to that by controls. ABT-239's effect on spatial memory retention in FAE rats was dose dependent. Conclusions:, These results suggest that ABT-239 administered prior to training can improve retention of acquired information by FAE offspring on more challenging versions of hippocampal-sensitive learning tasks. Further, the differential effects of ABT-239 in FAE offspring compared to controls raises questions about the impact of fetal ethanol exposure on histaminergic neurotransmission in affected offspring. [source]

    Pharmacological effects of carcinine on histaminergic neurons in the brain

    BRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2004
    Zhong Chen
    Carcinine (, -alanyl histamine) is an imidazole dipeptide. The present study was designed to characterize the pharmacological effects of carcinine on histaminergic activity in the brain and on certain neurobehavior. Carcinine was highly selective for the histamine H3 receptor over H1 or H2 receptor (Ki (,M)=0.2939±0.2188 vs 3621.2±583.9 or 365.3±232.8 ,M, respectively). Carcinine at a dose of 20 mg kg,1 slightly increased histidine decarboxylase (HDC) activity in the cortex (from 0.186±0.069 to 0.227±0.009 pmol mg protein,1 min,1). In addition, carcinine (10, 20, and 50 mg kg,1) significantly decreased histamine levels in mice brain. Like thioperamide, a histamine H3 receptor antagonist, carcinine (20, 50 ,M) significantly increased 5-HT release from mice cortex slices, but had no apparent effect on dopamine release. Carcinine (20 mg kg,1) significantly inhibited pentylenetetrazole-induced kindling. This inhibition was completedly reversed by (R)- , -methylhistamine, a representative H3 receptor agonist, and , -fluromethylhistidine, a selective HDC inhibitor. Carcinine (20 mg kg,1) ameliorated the learning deficit induced by scopolamine. This amelioration was reversed by (R)- , -methylhistamine as evaluated by the passive avoidance test in mice. Like thioperamide, carcinine dose-dependently increased mice locomotor activity in the open-field test. The results of this study provide first and direct evidence that carcinine, as a novel histamine H3 receptor antagonist, plays an important role in histaminergic neurons activation and might be useful in the treatment of certain diseases, such as epilepsy, and locomotor or cognitive deficit. British Journal of Pharmacology (2004) 143, 573,580. doi:10.1038/sj.bjp.0705978 [source]

    Targeting of the central histaminergic system for treatment of obesity and associated metabolic disorders

    DRUG DEVELOPMENT RESEARCH, Issue 8 2006
    Kjell Malmlöf
    Abstract There is currently a need for effective pharmacological therapies for treatment of obesity. In this communication, the involvement of the neurotransmitter histamine in the regulation of food intake is reviewed, together with results obtained in animals with pharmacologically increased brain histamine levels. A survey of the literature reveals that histaminergic circuits, arising from nerve cell bodies in the tuberomammillary nucleus and projecting into the paraventricular nucleus, the arcuate nucleus, and the ventromedial hypothalamus, are strongly involved in regulation of food intake and possibly also energy expenditure. Current literature also suggests the histaminergic circuits connect to other neuronal pathways involved in the regulation of energy balance and body weight. Studies performed in rodents demonstrate that H3 receptor antagonists increase hypothalamic histamine and decrease food intake, which result in decreased body weight. Lipid oxidation is increased and, at higher doses, body fat is also decreased. These changes are associated with lower circulating levels of insulin during an oral glucose challenge suggesting an increase in insulin sensitivity. The effects on food intake have also been confirmed in pigs and rhesus monkeys. It can thus be concluded that results obtained with H3 antagonist in animals warrant future clinical studies to evaluate whether this principle is effective in the treatment of human obesity. Drug Dev. Res. 67:651,665, 2006. © 2006 Wiley-Liss, Inc. [source]

    Endogenous histamine in the medial septum,diagonal band complex increases the release of acetylcholine from the hippocampus: a dual-probe microdialysis study in the freely moving rat

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2002
    Lucia Bacciottini
    Abstract The effects of histaminergic ligands on both ACh spontaneous release from the hippocampus and the expression of c-fos in the medial septum,diagonal band (MSA-DB) of freely moving rats were investigated. Because the majority of cholinergic innervation to the hippocampus is provided by MSA-DB neurons, we used the dual-probe microdialysis technique to apply drugs to the MSA-DB and record the induced effects in the projection area. Perfusion of MSA-DB with high-KCl medium strongly stimulated hippocampal ACh release which, conversely, was significantly reduced by intra-MSA-DB administration of tetrodotoxin. Histamine or the H2 receptor agonist dimaprit, applied directly to the hippocampus, failed to alter ACh release. Conversely, perfusion of MSA-DB with these two compounds increased ACh release from the hippocampus. Also, thioperamide and ciproxifan, two H3 receptor antagonists, administered into MSA-DB, increased the release of hippocampal ACh, whereas R-,-methylhistamine, an H3 receptor agonist, produced the opposite effect. The blockade of MSA-DB H2 receptors, caused by local perfusion with the H2 receptor antagonist cimetidine, moderated the spontaneous release of hippocampal ACh and antagonized the facilitation produced by H3 receptor antagonists. Triprolidine, an H1 receptor antagonist, was without effect. Moreover, cells expressing c-fos immunoreactivity were significantly more numerous in ciproxifan- or thioperamide-treated rats than in controls, although no colocalization of anti-c-fos and anti-ChAT immunoreactivity was observed. These results indicate a role for endogenous histamine in modulating the cholinergic tone in the hippocampus. [source]

    Carbon-14 labelling of selective H3 receptor antagonists

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2005
    Steen K. Johansen
    Abstract The fast and efficient carbon-14 labelling of the three potent H3 antagonists NNC 38-1202, NNC 38-1384, and NNC 38-1401 is reported. The two-step synthetic sequence, which included a Knoevenagel reaction, provided the carbon-14-labelled compounds in 38,55% overall yield starting from [2- 14C]malonic acid. The compounds were all obtained in high radiochemical purity ( > 99%) and with high specific activity (55.8 mCi/mmol). Copyright © 2005 John Wiley & Sons, Ltd. [source]