ReceptorsSelective non-imidazole histamineAgonistsSynthesisBetahistineNeurotransmissionInhibitionRatsNonimidazoleNeurotransmitterGastric acid secretionPharmacologyPotentHistidine decarboxylaseNeuronalPharmacological profileAssayDopamineScopolamine-inducedPreclinicalPitolisantAnti-inflammatoryMolecular weightClinicalAlkaloidsClinicallyAstemizoleLevocetirizineIsoformsInflammatoryModulationNitrogenMast cellsMechanismHumanHydrochlorideBindingBrainBindStimulateStudiesIncreasesActivitySignificantlyCentral nervouTargetPropertiesTargets
Receptors14
- In addition, olanzapine significantly increased hepatic histamine H1 receptors, while O + B co-treatment significantly reversed them to normal levels. (edu.au)
- As a consequence of the wide distribution of muscarinic receptors in the body, significant systemic exposure to muscarinic antagonists is associated with effects such as dry mouth, constipation, mydriasis, urinary retention (all predominantly mediated via blockade of M 3 receptors) and tachycardia (mediated by blockade of M 2 receptors). (justia.com)
- In my blog entry https://itsokaytosecondguessdoctors.info/f/h3-histamine-receptors I discuss H3 histamine receptors and what can get affected if these receptors are activated. (itsokaytosecondguessdoctors.info)
- Until recently histamine was thought to act on three receptors - H1, H2 and H3. (eurekaselect.com)
- the pharmacological profile of the protein is quite different from other histamine receptors. (eurekaselect.com)
- 3 beta ( GSK-3β), N-methyl-D-aspartate (NMDA) receptor, monoamine oxidases (MAOs), metal ions in the brain, 5-hydroxytryptamine (5-HT) receptors, the third subtype of histamine receptor (H 3 receptor), to phosphodiesterases (PDEs), along with a summary of their respective relationship to the disease network. (encyclopedia.pub)
- Among the four G protein-coupled receptors (H1-H4) identified as mediators of the biologic effects of histamine, the H3 receptor (H3R) is distinguished for its almost exclusive expression in the nervous system and the large variety of isoforms generated by alternative splicing of the corresponding mRNA. (ox.ac.uk)
- The histamine receptors are a class of G protein-coupled receptors which bind histamine as their primary endogenous ligand. (targetmol.com)
- Pyrrolidines are found in many alkaloids and drug molecules for example antagonists of kappa-opioid, Histamine H3, Dopamine D4, receptors, and also as HIV reverse Transcriptase inhibitors. (enaminestore.com)
- Unlike the other histamine receptors, H3 receptors are expressed mainly on neurons of the peripheral and central nervous system where they control the synthesis and release of histamine and also influence the release of other neurotransmitters including dopamine, γ-aminobutyric acid, noradrenaline, acetylcholine, serotonin and tachykinins. (drugdiscoveryopinion.com)
- Histamine signalling through H1 and H2 receptors increases the susceptibility of mice to infection with lethal strains of Plasmodium berghei and mice genetically deficient in the histidine decarboxylase gene - and thus lacking histamine - are highly resistant to severe malaria whether infected by mosquito bites or via injection of infected erythrocytes. (drugdiscoveryopinion.com)
- H3 receptors tightly regulate release of histamine and other neurotransmitters and neuronal histamine activity was found to be significantly higher in naive knockout mice than in wild type mice. (drugdiscoveryopinion.com)
- Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. (bvsalud.org)
- Many of the clinical presentations seen in anaphylaxis are due to activation of multiple histamine receptors. (medscape.com)
Selective non-imidazole histamine1
- JNJ-7777120 is the first potent and selective non-imidazole histamine H4 receptor antagonist with Ki of 4.5 nM, exhibits >1000-fold selectivity over the other hi. (targetmol.com)
Agonists3
- Potent selective H4 receptor agonists and antagonists have been synthesized and in vivo studies have indicated their action on H4 receptor. (eurekaselect.com)
- In some microdialysis experiments it had been showed that histamine as well as the H3 receptor agonists microdialysis connected with procognitive efficiency in behavioural pet versions. (tech-strategy.org)
- These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. (uea.ac.uk)
Synthesis3
- Hipskind, PA Synthesis and SAR of novel histamine H3 receptor antagonists. (bindingdb.org)
- Synthesis and pharmacological characterisation of new H2-antagonists containing NO-donor moieties, endowed with mixed antisecretory and gastroprotective activities. (unito.it)
- Thioperamide maleate is an effective and selective antagonist of H3 receptor (Ki = 4.3 nM) for inhibition of [3H]histamine synthesis (Ki = 31 nM). (targetmol.com)
Betahistine3
- Both animal and clinical studies have shown that co-treatment with betahistine (a histamine H1 receptor agonist/H3 receptor antagonist) is effective in controlling olanzapine-induced weight gain. (edu.au)
- Evidence suggesting that the histamine H3 receptor plays a key role in vestibular compensation comes from studies indicating that betahistine, a histamine-like drug that acts as both a partial histamine H1 receptor agonist and an H3 receptor antagonist, can accelerate the process of vestibular compensation. (uni-frankfurt.de)
- Betahistine hydrochloride is a histamine analog and H1 receptor agonist that serves as a vasodilator. (targetmol.com)
Neurotransmission1
- Histamine plays a role in a variety of physiological processes including allergic reactions, gastric acid secretion, bronchoconstriction and neurotransmission. (drugdiscoveryopinion.com)
Inhibition2
- Inhibition of electrically evoked [3H]serotonin from rat cortical pieces by histamine was antagonized with the blended H2/H3 receptor agonist/antagonists burimamide and impromidine the afterwards evoking discharge alone (Schlicker demo SB 202190 of H3 receptor-mediated serotonin discharge means significant effects continues to be to become driven. (tech-strategy.org)
- Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. (uea.ac.uk)
Rats4
- Structurally novel histamine H3 receptor antagonists GSK207040 and GSK334429 improve scopolamine-induced memory impairment and capsaicin-induced secondary allodynia in rats. (ox.ac.uk)
- Malmlöf K, Golozoubova V, Peschke B, Wulff BS, Refsgaard HH, Johansen PB, Cremers T, Rimvall K. Increase of neuronal histamine in obese rats is associated with decreases in body weight and plasma triglycerides. (wikipedia.org)
- Anticonvulsant and procognitive properties of the non-imidazole histamine H3 receptor antagonist DL77 in male adult rats. (krakow.pl)
- Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. (uea.ac.uk)
Nonimidazole2
- Anticonvulsive effect of nonimidazole histamine H3 receptor antagonists. (krakow.pl)
- Pitolisant(CAT: I003332) is a novel and selective nonimidazole inverse agonist at the recombinant human H3 receptor. (musechem.com)
Neurotransmitter6
- Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. (wikipedia.org)
- however, in recent years, histamine has been recognized as a central neurotransmitter. (wikipedia.org)
- Histamine is a monoamine neurotransmitter. (wikipedia.org)
- Non-mast cell histamine is found in several tissues, including the hypothalamus region of the brain, where it functions as a neurotransmitter. (wikipedia.org)
- Alexander hybridization (Pillot hybridization strategies claim that the H3(445) and H3(397) isoforms predominate in lots of human brain areas (Drutel and (Morisset and/or neurotransmitter discharge research (summarized in Desk 2). (tech-strategy.org)
- Histamine is a biogenic amine which acts as a mediator of immune responses as well as acting as a neurotransmitter in the CNS. (drugdiscoveryopinion.com)
Gastric acid secretion1
- Lafutidine is a newly developed histamine H(2)-receptor antagonist, which can inhibit gastric acid secretion. (targetmol.com)
Potent1
- At the human recombinant H(3) receptor, GSK207040 and GSK334429 were potent functional antagonists (pA(2)=9.26+/-0.04 and 8.84+/-0.04, respectively versus H(3) agonist-induced changes in cAMP) and exhibited inverse agonist properties (pIC(50)=9.20+/-0.36 and 8.59+/-0.04 versus basal GTPgammaS binding). (ox.ac.uk)
Histidine decarboxylase2
- Histamine is derived from the decarboxylation of the amino acid histidine, a reaction catalyzed by the enzyme L-histidine decarboxylase. (wikipedia.org)
- Bacteria also are capable of producing histamine using histidine decarboxylase enzymes unrelated to those found in animals. (wikipedia.org)
Neuronal1
- It is my pleasure to announce the last activity organised by the EHRS this year, which is a Festive Virtual Poster Event focused on Neuronal Histamine to be held on Thursday 16 December 2021 at 12.00 noon CET (expected duration: 1h 30min). (ehrs.org.uk)
Pharmacological profile2
- Accordingly, there is still a need for improved M 3 receptor antagonists that would have an appropriate pharmacological profile, for example in term of potency, pharmacokinetics or duration of action. (justia.com)
- There is a need for M 3 receptor antagonists that would have a pharmacological profile suitable for an administration by the inhalation route. (justia.com)
Assay1
- 2010. Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists. . (cornell.edu)
Dopamine2
- Whereas the selective H3 receptor antagonist GSK189254 was proven to evoke ACh dopamine and norepinephrine discharge within the rat cingulate cortex there is no influence on serotonin (Medhurst microdialysis studies also show that ABT-239 boosts cortical and hippocampal ACh at dosages (0.1-3.0?mg?kg?1) and period classes (30-120?min) that parallel the behavioural efficiency in cognitive versions. (tech-strategy.org)
- Ritanserin is a highly effective, relatively selective, long-acting antagonist of 5-HT2 receptor (IC50: 0.9 nM), less active on Histamine H1, Dopamine D2, Adren. (targetmol.com)
Scopolamine-induced1
- 2007 These substances are powerful antagonists on the rat H3 receptor ( K i=1 and 0.8 respectively) that reversed scopolamine-induced amnesia within the inhibitory avoidance ensure that you significantly reversed capsaicin-induced decrease in the paw withdrawal. (tech-strategy.org)
Preclinical1
- The released preclinical data are in keeping with the power of H3 antagonists to boost cognition. (tech-strategy.org)
Pitolisant2
- Aculys Pharma, Inc. ("Aculys Pharma" Headquarters: Fujisawa City, Kanagawa Prefecture, Representative Director and CEO: Kazunari Tsunaba), a biopharmaceutical company focused on the development and commercialization of new innovative drugs in the fields of neurology and psychiatry, announced that it has initiated a Phase 1 clinical trial of histamine H3 receptor antagonist / inverse agonist, pitolisant (development code: BF2.649) in Japan, and the first dose was administered successfully in January 2022. (catalyspacific.com)
- Pitolisant is an antagonist / inverse agonist that selectively binds to the histamine H3 receptor, an autoreceptor located in the presynaptic region of the histamine containing neurons in the human brain that plays a critical role in regulating sleep and wake rhythm. (catalyspacific.com)
Anti-inflammatory2
- In addition, anti-inflammatory effects of H4 receptor antagonists, with special emphasis to JNJ7777120, a selective H4 receptor antagonist have been focused exhaustively. (eurekaselect.com)
- The H1 receptor mediates most of the pro-inflammatory effects of histamine whereas the anti-inflammatory and immunosuppressive activities of histamine are mainly dependent on stimulation of the H2 receptor. (drugdiscoveryopinion.com)
Molecular weight1
- Histamine, a low molecular weight amine has been extensively studied for its various pharmacological profiles. (eurekaselect.com)
Clinical2
- Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. (sri.com)
- In wild type mice, both the H1 receptor antagonist, levocetirizine, and the H2 receptor antagonist, cimetidine, were found to be effective in reducing clinical symptoms and mortality caused by cerebral malaria. (drugdiscoveryopinion.com)
Alkaloids1
- Certain amines and alkaloids, including such drugs as morphine, and curare alkaloids, can displace histamine in granules and cause its release. (wikipedia.org)
Clinically1
- A commonly reported side-effect following inhaled administration of therapeutic dose of the current, clinically used non-selective muscarinic antagonists is dry-mouth and while this is reported as only mild in intensity it does limit the dose of inhaled agent given. (justia.com)
Astemizole1
- In contrast, astemizole acts as a histamine H1 receptor (H1R1) antagonist to activate T cells in a non-specific, DC-independent fashion. (bmj.com)
Levocetirizine3
- Levocetirizine is a Histamine-1 Receptor Antagonist. (targetmol.com)
- The mechanism of action of levocetirizine is as a Histamine H1 Receptor Antagonist. (targetmol.com)
- The beneficial role of the H3 receptor in controlling histamine levels and limiting disease was demonstrated by the higher effectiveness of cimetidine and, to a lesser extent, levocetirizine in wild type compared with H3 receptor knockout mice. (drugdiscoveryopinion.com)
Isoforms1
- Results: Expression levels for histamine H3 receptor (total) as well as three isoforms which display variable lengths of the third intracellular loop of the receptor were analyzed using in situ hybridization on brain sections containing the rat medial vestibular nucleus after unilateral labyrinthectomy. (uni-frankfurt.de)
Inflammatory2
- Histamine is involved in the inflammatory response and has a central role as a mediator of itching. (wikipedia.org)
- A study recently published in the journal PLoS ONE has now investigated the role of the H3 receptor in the inflammatory response in the brain during P. berghei infection in mice. (drugdiscoveryopinion.com)
Modulation1
- Levodropropizine can inhibit histamine receptor, anti-allergic, and reduce a cough by modulation of neuropeptides involved in the cough reflex and by interfering. (targetmol.com)
Nitrogen4
- In aqueous solution, the imidazole ring of histamine exists in two tautomeric forms, identified by which of the two nitrogen atoms is protonated. (wikipedia.org)
- Histamine has two basic centres, namely the aliphatic amino group and whichever nitrogen atom of the imidazole ring does not already have a proton. (wikipedia.org)
- Since human blood is slightly basic (with a normal pH range of 7.35 to 7.45) therefore the predominant form of histamine present in human blood is monoprotic at the aliphatic nitrogen. (wikipedia.org)
- Regarding this, this project aims to synthesize and evaluate the activity of a set of anilidoalkylpiperzines with variations in the aromatic ring, the length of the alkyl chain and also in the terminal nitrogen as anticholinesterase agents and as antagonists of the histamine H3 receptor. (fapesp.br)
Mast cells3
- As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. (wikipedia.org)
- Most histamine in the body is generated in granules in mast cells and in white blood cells (leukocytes) called basophils. (wikipedia.org)
- Histamine is released by mast cells as an immune response and is later degraded primarily by two enzymes: diamine oxidase (DAO), coded by AOC1 genes, and histamine-N-methyltransferase (HNMT), coded by the HNMT gene. (wikipedia.org)
Mechanism1
- The most important pathophysiologic mechanism of mast cell and basophil histamine release is immunologic. (wikipedia.org)
Human2
- Merely a decade back, sequencing of human genome has revealed a new histamine receptor - H4 receptor. (eurekaselect.com)
- In human infection with Plasmodium falciparum , as well as in murine models of malaria, increased levels of histamine have been shown to be associated with severity of infection. (drugdiscoveryopinion.com)
Hydrochloride2
- Histamine base, obtained as a mineral oil mull, melts at 83-84 °C. Hydrochloride and phosphorus salts form white hygroscopic crystals and are easily dissolved in water or ethanol, but not in ether. (wikipedia.org)
- Clemizole hydrochloride is an antagonist for H1 histamine receptor. (targetmol.com)
Binding3
- We compared these expression levels to H3 receptor binding densities. (uni-frankfurt.de)
- Coinciding with the decreasing trends in H3 receptor mRNA levels was an observed increase in H3 receptor binding densities occurring in the ipsilateral medial vestibular nuclei 48 h post-lesion. (uni-frankfurt.de)
- This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. (uea.ac.uk)
Brain2
- It acts as a histamine H3 receptor antagonist/inverse agonist, which modulates the release of various neurotransmitters in the brain. (musechem.com)
- Compared with wild type mice, mice deficient in the H3 receptor showed an accelerated onset of cerebral malaria, increased brain pathology and more pronounced loss of blood brain barrier integrity associated with earlier death. (drugdiscoveryopinion.com)
Bind1
- Histamine release occurs when allergens bind to mast-cell-bound IgE antibodies. (wikipedia.org)
Stimulate2
- Antibiotics like polymyxin are also found to stimulate histamine release. (wikipedia.org)
- Osthole, a potential inhibitor of histamine H1 receptor, has been shown to stimulate osteoblast proliferation and differentiation. (targetmol.com)
Studies2
- Anticonvulsant and reproductive toxicological studies of the imidazole-based histamine H3R antagonist 2-18 in mice. (krakow.pl)
- In further studies, the H3 receptor agonist, (R)-alpha-methylhistamine, was found to be effective in reducing progression to cerebral malaria. (drugdiscoveryopinion.com)
Increases1
- Histamine increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues. (wikipedia.org)
Activity1
- H1 and H3 activity results in cutaneous itch and nasal congestion. (medscape.com)
Significantly1
- In more pathophysiologically relevant pharmacodynamic models, GSK207040 (0.1, 0.3, 1 and 3mg/kg p.o.) and GSK334429 (0.3, 1 and 3mg/kg p.o.) significantly reversed amnesia induced by the cholinergic antagonist scopolamine in a passive avoidance paradigm. (ox.ac.uk)
Central nervou1
- In the central nervous system, histamine released into the synapses is primarily broken down by histamine-N-methyltransferase, while in other tissues both enzymes may play a role. (wikipedia.org)
Target1
- histamine H3 receptor first referred to in 1983 like a histamine autoreceptor and later on proven to also work as a heteroreceptor that regulates the discharge of other neurotransmitters has been the focus of research by numerous laboratories since it represents a stylish drug target for several indications including cognition. (tech-strategy.org)