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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BP1.3656B
0 ImagesCat. No.: HY-181960CAS No.: 914302-78-6BP1.3656B is a selective, orally active, blood-brain barrier-permeable histamine H3 receptor (histamine H3 receptor) inverse agonist/antagonist, with a KB value of 0.08 nM for antagonizing agonist-induced activity and an IC50 value of 0.38 nM for directly inhibiting the basal activity of the receptor. BP1.3656B reduces alcohol consumption, alcohol-seeking behavior, alcohol self-administration, motivation to drink, alcohol relapse, alcohol-induced hyperlocomotion, and binge alcohol intake. BP1.3656B is applicable for the research of alcohol use disorder.
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Irdabisant hydrochloride
0 ImagesCat. No.: HY-109968ACAS No.: 1005398-61-7Synonyms: CEP-26401 hydrochlorideIrdabisant (CEP-26401) hydrochloride is a selective, orally active and blood-brain barrier (BBB) penetrant histamine H3 receptor (H3R) inverse agonist/inverse agonist with Ki values of 7.2 nM and 2.0 nM for rat H3R and human H3R, respectively. Irdabisant hydrochloride has relatively low inhibitory activity against hERG current with an IC50 of 13.8 μM. Irdabisant hydrochloride has cognition-enhancing and wake-promoting activities in the rat social recognition model. Irdabisant hydrochloride can be used to research schizophrenia or cognitive impairment.
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JNJ-28583867
0 ImagesCat. No.: HY-119087CAS No.: 892407-39-5JNJ-28583867 is an orally active and selective histamine H3 receptor antagonist (Ki=10.6 nM) and serotonin transporter (SERT) inhibitor (Ki=3.7 nM). JNJ-28583867 can be used in the research of depression.
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VUF5207
0 ImagesCat. No.: HY-119056CAS No.: 397248-39-4VUF5207, an Impentamine (HY-107564) analogue, is a partial agonist of histamine H3 receptor.
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Proxyfan Oxalate
0 ImagesCat. No.: HY-107557ACAS No.: 1620017-81-3Proxyfan Oxalate 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 Oxalate is over 1000-fold more potent at H3 receptors than other histamine receptors.
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FUB 465
0 ImagesCat. No.: HY-124147CAS No.: 184028-93-1FUB 465 is an orally active inverse agonist at the constitutively active histamine H3 receptor with a pKi of 6.2 for H3 receptor. FUB 465 can be used in the research of central nervous system diseases.
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H3R antagonist 5
0 ImagesCat. No.: HY-14517CAS No.: 879368-27-1H3R antagonist 5 (Compound 1b) is a selective histamine H3 receptor inverse agonist with a IC50 of 0.54 nM and the ability to cross the blood-brain barrier. H3R antagonist 5 can be used in central nervous system-related research.
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Carcinine
0 ImagesCat. No.: HY-107567CAS No.: 56897-53-1Synonyms: β-AlanylhistamineCarcinine (β-Alanylhistamine) 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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Clobenpropit
0 ImagesCat. No.: HY-115447CAS No.: 145231-45-4Clobenpropit is a potent histamine H3-receptor antagonist. Clobenpropit decreases dopamine release and increases histamine levels in the hypothalamus. Clobenpropit shows antipsychotic-like activities. Clobenpropit causes a resuscitating effect in rats subjected to the hemorrhagic shock.
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A-423579
0 ImagesCat. No.: HY-12192CAS No.: 461045-17-0A-423579 is an orally active non-imidazole histamine H3 receptor antagonist. A-423579 exhibits high affinity and good selectivity for human and rat H3 receptors, and possesses both antagonistic and inverse agonistic activities. A-423579 can effectively reduce body weight in obese rodents, with concomitant decreases in fat content, plasma leptin levels, and triglycerides. A-423579 possesses anti-obesity activity and can be used in the research of obesity and related metabolic disorders.
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LINS05414
0 ImagesCat. No.: HY-181597LINS05414 is a histamine H3 receptor ligand with antiCholinesterase and metal chelating activities. LINS05414 exhibits inhibitory activity against acetylcholinesterase (pIC50 = 4.03) and butyrylcholinesterase (pIC50 = 3.83), with a pKi of 6.37 for human histamine H3 receptors. LINS05414 chelates copper ions, ferrous ions and ferric ions. LINS05414 regulates the release of neurotransmitters. LINS05414 can be used in the research of neurodegenerative diseases.
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BP 2-94
0 ImagesCat. No.: HY-137090CAS No.: 139191-80-3Synonyms: BP 2.94BP 2-94 (BP 2.94) is an orally active and highly selective prodrug targeting the histamine H3 receptor. BP 2-94 exerts anti-inflammatory, analgesic and antinociceptive effects by inhibiting histamine release and modulating neurogenic inflammation. BP 2-94 is promising for research of asthma, migraines, and inflammatory pain-related disorders.
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H3R antagonist 2
0 ImagesCat. No.: HY-146383CAS No.: 2970985-05-6H3R antagonist 2 (Compound 23) is a multitarget histamine H3 receptor (H3R) antagonist with a Ki of 170 nM for hH3R . H3R antagonist 2 shows inhibitory effects with IC50 values of 180, 880 and 775 nM for acetylcholinesterase, butyrylcholinesterase and human monoamine oxidase B (hMAO B), respectively. H3R antagonist 2 shows favorable anti-neuropathic pain and memory-enhancing effects. H3R can across BBB.
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FUB 349
0 ImagesCat. No.: HY-123278CAS No.: 184023-52-7FUB 349 (Compound 8) is a selective Aromatase inhibitor with an IC50 of 12 μM. FUB 349 is also a H3 receptor antagonist with Kis of 12 and 2.1 nM for rH3R and hH3R, respectively. FUB 349 can be used for neurological diseases such as cognitive impairment research.
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GR-175737
0 ImagesCat. No.: HY-123447CAS No.: 176860-26-7GR 175737 is a partial histamine H3 receptor agonist, with an EC50 of 7.8 nM. GR 175737 can be used in the research of inflammatory diseases.
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Bavisant dihydrochloride
0 ImagesCat. No.: HY-14880ACAS No.: 929622-09-3Synonyms: JNJ-31001074 dihydrochlorideBavisant (JNJ-31001074) dihydrochloride is an orally active, potent, brain-penetrating and highly selective antagonist of the histamine H3 receptor. Bavisant dihydrochloride can be used for attention-deficit hyperactivity disorder (ADHD) research.
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A-317920
0 ImagesCat. No.: HY-122171CAS No.: 360551-59-3A-317920 is a selective and potent rat histamine H3 receptor (H3R) antagonist with pKi value of 9.2 and 7.0 for full-length rat and full-length human H3R, respectively. A-317920 exhibits over 130 fold selective affinity for the rat over the human H3R. A-317920 enhances cognition via H3R blockade.
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VUF 5681 dihydrobromide
0 ImagesCat. No.: HY-107556CAS No.: 639089-06-8VUF 5681 dihydrobromide is a neutral antagonist of histamine H3 receptor. VUF 5681 dihydrobromide also has partial agonist function of H3 receptor. VUF 5681 dihydrobromide blocks the effects of Thioperamide (HY-12206). VUF 5681 dihydrobromide is used in central nervous system disease research.
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GSK334429
0 ImagesCat. No.: HY-116386CAS No.: 799557-57-6GSK334429 is a selective and orally active non-imidazole histamine H3 receptor antagonist with a pKi of 9.49 against human H3 receptor. GSK334429 can be utilized in neurological research.
