Disease relevance of Hrh3

• Therapeutic potential of histamine H3 receptor agonist for the treatment of obesity and diabetes mellitus [1].
• Impaired drinking response in histamine H3 receptor knockout mice following dehydration or angiotensin-II challenge [2].
• A discrete and novel region of the posterior arcuate nucleus, the dorsal medial posterior arcuate nucleus (dmpARC) has been identified, where a battery of gene expression changes for signalling molecules (vgf and histamine H3 receptor) and transcription factors (RXRgamma and RAR) occur in association with seasonal changes in body weight [3].

Psychiatry related information on Hrh3

• Thioperamide, the selective histamine H3 receptor antagonist, attenuates stimulant-induced locomotor activity in the mouse [4].
• The participation of histamine in the actions of tacrine and the relevance of histamine H3 receptor antagonists in Alzheimer's disease are suggested [5].
• Histamine H3 receptor antagonists/inverse agonists have been proposed as potential therapeutic agents for the treatment of a number of neurological disorders ranging from attention deficit hyperactivity disorder and Alzheimer's disease to narcolepsy and schizophrenia [6].
• The interaction of selective histamine H3-receptor agonist R(alpha)-methyl-histamine (RAMH) and antagonist thioperamide (THP) with some antiepileptic drugs [AED; phenytoin (PHT), carbamazepine (CBZ), sodium valproate (SVP), and gabapentin (GBP)] was studied on seizures induced by maximal electroshock (MES) and pentylenetetrazole (PTZ) in mice [7].

High impact information on Hrh3

• In the developing mouse brain, histamine H3 receptor blockade, which increases histamine release, has detrimental sex-dependent effects on object recognition, spatial learning in the water maze, and pre-pulse inhibition in adulthood [8].
• Histamine H3 receptor agonist Nalpha-methylhistamine and antagonist thioperamide had no effect [9].
• Synthesis, X-ray crystallography, and pharmacokinetics of novel azomethine prodrugs of (R)-alpha-methylhistamine: highly potent and selective histamine H3 receptor agonists [10].
• Azomethine derivatives of the highly potent histamine H3 receptor agonist (R)-alpha-methylhistamine (1) were prepared as lipophilic prodrugs to improve the bioavailability of the hydrophilic drug, particularly its entry into the brain [10].
• 2 Carcinine was highly selective for the histamine H3 receptor over H1 or H2 receptor (Ki (microM)=0.2939+/-0.2188 vs 3621.2+/-583.9 or 365.3+/-232.8 microM, respectively) [11].

Biological context of Hrh3

• The conserved sequences of the mouse histamine H3 receptor at the potential alternative splice junctions suggest that the splice isoforms found in guinea pig, rat, human, and hamster may also be present in the mouse [12].
• Structure-activity relationships of novel azomethine prodrugs of the histamine H3-receptor agonist (R)-alpha-methylhistamine: from alkylaryl to substituted diaryl derivatives [13].
• On the basis of recently described diary limine prodrugs of the histamine H3-receptor agonist (R)-alpha-methylhistamine (1) as a series of new azomethine prodrugs containing five- and six-membered heterocycles were synthesized and tested for their in vitro hydrolysis rates and in vivo activity after oral application [14].

Anatomical context of Hrh3

• Histamine H3 receptor ligands have been proposed to be of potential therapeutic interest for the treatment of different central nervous system disorders; however, the psychopharmacological properties of these drugs have not been studied extensively [15].
• Binding of histamine H3-receptor antagonists to hematopoietic progenitor cells. Evidence for a histamine transporter unrelated to histamine H3 receptors [16].
• To determine whether negative feedback regulation of the histamine H3 receptor-mediated effect might occur, we tested the effects of steroid treatment upon binding of the agonist [3H]N alpha-methylhistamine to AtT-20 cell membranes [17].
• These results identify, for the first time, a cell line expressing H3 receptors and indicate that the high affinity histamine H3 receptor regulates ACTH release from that cell [18].
• This effect was antagonized by BP 2.94 (10 mg/kg, i.p.), a prodrug of (R)-alpha-methylhistamine (histamine H3-receptor agonist), and by ketotifen (4 mg/kg, i.p.), a histamine H1-receptor antagonist, both penetrating the blood-brain barrier [19].

Associations of Hrh3 with chemical compounds

• 4 Like thioperamide, a histamine H3 receptor antagonist, carcinine (20, 50 microM) significantly increased 5-HT release from mice cortex slices, but had no apparent effect on dopamine release [11].
• Clobenpropit (VUF-9153), a new histamine H3 receptor antagonist, inhibits electrically induced convulsions in mice [20].
• Replacement of imidazole by a piperidine moiety differentially affects the potency of histamine H3-receptor antagonists [21].
• The histamine H3 receptor agonist R(-)alpha-methylhistamine (RAMH, 10 mg/kg) did not significantly modify the nefopam analgesic activity in the writhing test [22].
• Synergistic interaction between fentanyl and the histamine H3 receptor agonist R-(alpha)-methylhistamine, on the inhibition of nociception and plasma extravasation in mice [23].

Physical interactions of Hrh3

• The ability of histamine H3 receptor ligands to interact with 5-HT3 receptors in NG108-15 cells was studied using the whole cell patch clamp recording technique [24].

Other interactions of Hrh3

• 8 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 [11].
• Effects of the histamine H3 receptor ligands thioperamide and (R)-alpha-methylhistamine on histidine decarboxylase activity of mouse brain [25].
• Effects of iodoproxyfan, a potent and selective histamine H3 receptor antagonist, on alpha 2 and 5-HT3 receptors [26].
• Swiss strain albino mice were treated with different doses of histamine H3-receptor antagonist thioperamide (3.75, 7.5 and 15 mg/kg intraperitoneally) and agonist (R)-alpha-methylhistamine (5 microg intracerebroventricularly) [27].

Analytical, diagnostic and therapeutic context of Hrh3

• Benzophenone derivatives and related compounds as potent histamine H3-receptor antagonists and potential PET/SPECT ligands [28].

References