H3 Receptor
H3 receptor functions as a presynaptic histamine autoreceptor that inhibits histamine release in rat cerebral cortex, defining a receptor class pharmacologically distinct from H1 and H2 receptors[1]. Mechanistically, H3 receptor signaling regulates neurotransmitter release, placing HRH3 in central synaptic modulation relevant to cognition, wakefulness, and sleep regulation[2]. In disease-focused research, H3 receptor antagonists and inverse agonists support experimental designs for central nervous system disorders because blocking this inhibitory receptor can increase histaminergic neuronal activity[2][5]. Compared with related H3 receptor isoforms, human HRH3 shows extensive alternative splicing, and several cloned variants from human thalamus are coexpressed in human brain[3][4]. This isoform diversity has practical importance because functional human H3 receptor isoforms show different agonist potency profiles, including increased potency at isoform 2 relative to isoform 1[3]. For experimental applications, thioperamide and (R)-α-methylhistamine were described as selective H3-autoreceptor ligands, while pitolisant represents an H3 receptor inverse agonist advanced into clinical studies for narcolepsy[5][6].
References:
- [1]. Arrang JM, et al. Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature. 1983 Apr 28;302(5911):832-7. [Content Brief]
- [2]. Esbenshade TA, et al. The histamine H3 receptor: an attractive target for the treatment of cognitive disorders. Br J Pharmacol. 2008 Jul;154(6):1166-81. [Content Brief]
- [3]. Wellendorph P, et al. Molecular cloning and pharmacology of functionally distinct isoforms of the human histamine H(3) receptor. Neuropharmacology. 2002 Jun;42(7):929-40. [Content Brief]
- [4]. Francis COGÉ, et al. Genomic organization and characterization of splice variants of the human histamine H3 receptor. Biochem J 15 April 2001; 355 (2): 279-288.
- [5]. Schwartz JC. The histamine H3 receptor: from discovery to clinical trials with pitolisant. Br J Pharmacol. 2011 Jun;163(4):713-21. doi: 10.1111/j.1476-5381.2011.01286.x. PMID: 21615387; PMCID: PMC3111674. et al. The histamine H3 receptor: from discovery to clinical trials with pitolisant. Br J Pharmacol. 2011 Jun;163(4):713-21. [Content Brief]
- [6]. Dauvilliers Y, et al. Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Lancet Neurol. 2013 Nov;12(11):1068-75. [Content Brief]
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H3 Receptor Related Products (60)
Related Products (60)
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JNJ10191584
0 ImagesSynonyms: VUF6002JNJ10191584 (VUF6002) is an orally active and selective histamine H4 receptor antagonist with a Ki value of 26 nM. JNJ10191584 shows 540-fold selectivity to H4 receptor over H3 receptor with a Ki value of 14.1 μM. JNJ10191584 inhibits chemotaxis of eosinophils and mast cells with IC50 values of 530 nM and 138 nM, respectively.
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Thioperamide maleate
0 ImagesSynonyms: MR-12842 maleateThioperamide maleate (MR-12842 maleate) is a potent, orally available, brain penetrant and selective H3 receptor antagonist with a Ki of 4.3 nM for inhibition of [3H]histamine release. Thioperamide maleate inhibits [3H]histamine synthesis with a Ki of 31 nM.
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PF-03654746 Tosylate
0 ImagesPF-03654746 Tosylate is a potent, selective and brain-penetrant histamine H3 receptor antagonist. PF-03654746 Tosylate reduces allergen-induced nasal symptoms. PF-03654746 Tosylate has potential for treatment of human cognitive disorders, improves cognitive efficacy and disease-modifying effects in Alzheimer's disease (AD).
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H3R antagonist 1 hydrochloride
0 ImagesH3R antagonist 1 hydrochloride is a histamine receptor 3 (H3R) inverse agonist. H3R antagonist 1 hydrochloride increases the expression levels of myelin-associated glycoprotein (MAG) and myeline basic protein (MBP) in differentiating oligodendrocytes. H3R antagonist 1 hydrochloride can be used for the study of multiple sclerosis.
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(R)-(-)-α-Methylhistamine dihydrobromide
0 ImagesCat. No.: HY-100999CAS No.: 868698-49-1(R)-(-)-α-Methylhistamine dihydrobromide is a potent, selective and brain-penetrant agonist of H3 histamine receptor, with a Kd of 50.3 nM. (R)-(-)-α-Methylhistamine dihydrobromide can enhance memory retention, attenuates memory impairment in rats.
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Carcinine dihydrochloride
0 ImagesSynonyms: β-Alanylhistamine dihydrochlorideCarcinine (β-Alanylhistamine) dihydrochloride is the dihydrochloride salt of Carcinine (HY-107567). Carcinine is a selective and orally active histamine H3 receptor antagonist with a Ki of 0.2939 μM. Carcinine can reduce histamine content. Carcinine exhibits anti-oxidant activity and neuroprotective effects. Carcinine shows positive inotropic effect and can reduce blood sugar and blood lipid levels. Carcinine can be used for the researches of inflammation, neurological, cardiovascular and metabolic disease, such as retinal damage, seizure and diabetes.
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Proxyfan
0 ImagesProxyfan is a potent histamine H3 receptor antagonist with Ki values of 2.9 nM and 2.7 nM for rat and human H3 receptor, respectively. Proxyfan is over 1000-fold more potent at H3 receptors than other histamine receptors.
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Betahistine mesylate
0 ImagesBetahistine mesylate is an orally active histamine H1 receptor agonist and a H3 receptor antagonist. Betahistine mesylate is used for the study of rheumatoid arthritis (RA).
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Cipralisant
0 ImagesSynonyms: GT-2331Cipralisant (GT-2331) is an orally active, low-toxicity, potent, selective, high affinity histamine H3 receptor full antagonist in vivo, and an agonist in vitro, with a pKi of 9.9 for histamine H3 receptor and a Ki of 0.47 nM for rat histamine H3 receptor. Cipralisant has the potential for attention-deficit hyperactivity disorder research. Cipralisant is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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MK-0249
0 ImagesMK-0249 (Compound 1) is a potent, selective and orally active histamine H3 receptor antagonist, with an IC50 of 1.7 nM for human H3.
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JNJ10191584 maleate
0 ImagesCat. No.: HY-107558CAS No.: 869497-75-6Synonyms: VUF6002 maleateJNJ10191584 (VUF6002) maleate (compound 40) is an orally active and selective histamine H4 receptor antagonist with a Ki value of 26 nM. JNJ10191584 maleate shows 540-fold selectivity to H4 receptor over the H3 receptor with a Ki value of 14.1 μM. JNJ10191584 maleate inhibits chemotaxis of eosinophils and mast cells with IC50 values of 530 nM and 138 nM, respectively.
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H3R antagonist 6
0 ImagesCat. No.: HY-175367CAS No.: 2183338-59-0H3R antagonist 6 (Compounds 3) (H3-2406) is a Histamine receptor 3 (H3R) antagonist with an IC50 of 5.6 nM. H3R antagonist 6 labeled with 18F has high radiochemical yield, molar activity and moderate brain uptake, but with an off-target binding to the Sigma-1 receptor. H3R antagonist 6 can be used as a PET radioligand for positron emission tomography imaging for central nervous system (CNS) disorders research.
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Cipralisant maleate
0 ImagesSynonyms: GT-2331 maleateCipralisant (GT-2331) (maleate) is an orally active, low-toxicity, potent, selective, high affinity histamine H3 receptor full antagonist in vivo, and an agonist in vitro, with a pKi of 9.9 for histamine H3 receptor and a Ki of 0.47 nM for rat histamine H3 receptor. Cipralisant (maleate) has the potential for attention-deficit hyperactivity disorder research. Cipralisant (maleate) is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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σ1R/H3R ligand-1
0 ImagesCat. No.: HY-181722σ1R/H3R ligand-1 is a dual σ1R/H3R antagonist with a σ1R Ki of 8.8 nM and an H3R Ki of 31.2 nM. Through the dual action of simultaneously antagonizing σ1R and H3R, σ1R/H3R ligand-1 exhibits potent dose-dependent analgesic activity in mouse models of visceral pain and neuropathic pain. σ1R/H3R ligand-1 can be used for the research of visceral pain and neuropathic pain.
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JNJ 10181457 dihydrochloride
0 ImagesCat. No.: HY-107562CAS No.: 544707-20-2JNJ-10181457 is a neutral, potent, brain-penetrant and selective non-imidazole H3 antagonist which increases NE and ACh concentrations in rat frontal cortex. JNJ-10181457 can be used for neurological research.
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ABT-288
0 ImagesCat. No.: HY-19881CAS No.: 948845-91-8ABT-288 is a competitive, potent and selective histamine H3 receptor (H3R) antagonist. ABT-288 has Ki values of 1.9 and 8.2 nM for human and rat H3Rs, respectively. ABT-288 can be used in cognitive impairment research..
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JNJ-5207852 dihydrochloride
0 ImagesJNJ-5207852 dihydrochloride is a selective and potent histamine H3 receptor (H3R) antagonist, with pKis of 8.9, 9.24 for rat and human H3R, respectively.
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H3R antagonist 8
0 ImagesCat. No.: HY-178016CAS No.: 3097193-89-7H3R antagonist 8 is a selective nonimidazole histamine H3 receptor antagonist (IC50 = 0.35 μM). H3R antagonist 8 exhibits hERG channel blockade activity (IC50 = 0.67 μM). H3R antagonist 8 inhibits seizures by antagonizing H3 receptor. H3R antagonist 8 reduces tonic hind limb extension (THLE) in mice in the maximal electroshock seizure (MES) model (ED50 = 20.21 mg/kg) and and shortens pentylenetetrazol (PTZ)-induced total movement distance in AB strain zebrafish larvae. H3R antagonist 8 can be used for the study of epilepsy.
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Betahistine EP Impurity C
0 ImagesBetahistine EP Impurity C (NSC19005) is an impurity of Betahistine. Betahistine is a potent, orally active and well-tolerated histamine H1 receptor agonist and H3 receptor antagonist used for the study of rheumatoid arthritis (RA).
