H₃ Receptor Antagonist

Amitriptyline hydrochloride is an orally active tricyclic antidepressant (TCA). Amitriptyline hydrochloride mainly exerts its antidepressant effect by blocking SERT (K_i = 3.45 nM) and NET (K_i = 13.3 nM), thereby increasing the concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in the synaptic cleft. Amitriptyline hydrochloride is also an agonist at α2A and TrkA/TrkB receptors, thereby exerting analgesic and neurotrophic activities (inhibiting cell apoptosis). Amitriptyline hydrochloride can reduce inflammation, angiogenesis and fibrosis. Amitriptyline hydrochloride binds to DAT (with K_i = 2.58 μM). Amitriptyline hydrochloride has high affinity for a series of receptors and can antagonize muscarinic cholinergic receptors (M1/M2/M3/M4/M5 receptors) (K_i = 11-24 nM), H1 receptors (K_i = 0.5-1.1 nM), adrenergic α1 receptors (K_i = 4.4 nM), etc., resulting in a series of side effects. Amitriptyline hydrochloride can block sodium channels and hERG potassium channel (IC₅₀ = 4.78 μM) and it has cardiotoxicity.

Pitolisant hydrochloride is a potent and selective nonimidazole inverse agonist at the recombinant human histamine H3 receptor (K_i=0.16 nM).

σ1R/H3R ligand-1 is a dual σ₁R/H₃R antagonist with a σ₁R K_i of 8.8 nM and an H₃R K_i 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.

BP1.3656B is a selective, orally active, blood-brain barrier-permeable histamine H3 receptor (histamine H3 receptor) inverse agonist/antagonist, with a K_B 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.

GSK239512 is a blood-brain barrier-permeable, orally active H3 receptor antagonist, with a human pK_i ranging from <5.5 to 9.92 and a murine pK_i ranging from 9.44 to 9.83. GSK239512 modulates cholinergic and monoaminergic neurotransmission, blocks the inhibitory feedback of H3 receptors, and increases the release of pro-cognitive neurotransmitters. GSK239512 induces oligodendrocyte precursor cell differentiation and restores myelin gene expression at the cellular level. GSK239512 reverses Scopolamine (HY-N0296)-induced memory deficits and improves recognition memory in animal models. GSK239512 can be used in research related to Alzheimer's disease, chronic traumatic encephalopathy, relapsing-remitting multiple sclerosis, and schizophrenia.

GSK189254A (GSK189254 free base) is a novel, potent and selective histamine H3 receptor antagonist with pK_i values of 9.59-9.90 and 8.51-9.17 for human and rat H3, respectively.

JNJ-5207852 is a selective and potent histamine H₃ receptor (H₃R) antagonist, with pK_is of 8.9, 9.24 for rat and human H₃R, respectively.

Ciproxifan maleate (FUB 359 maleate) is a potent, selective, orally bioavailable and competitive antagonist of histamine H₃-receptor, with an IC₅₀ of 9.2 nM. Ciproxifan maleate displays low apparent affinity at other receptor subtypes. Ciproxifan maleate can be used for the research of aging disorders and Alzheimer's disease.

Bavisant (JNJ-31001074) is an orally active, potent, brain-penetrating and highly selective antagonist of the histamine H₃ receptor. Bavisant can be used for attention-deficit hyperactivity disorder (ADHD) research.

Ciproxifan (FUB 359) is a potent, selective, orally bioavailable and competitive antagonist of histamine H₃-receptor, with an IC₅₀ of 9.2 nM. Ciproxifan displays low apparent affinity at other receptor subtypes. Ciproxifan can be used for the research of aging disorders and Alzheimer's disease.

ABT-239 is a novel, highly efficacious, non-imidazole class of H3R antagonist and a transient receptor potential vanilloid type 1 (TRPV1) antagonist.

Tiotidine (ICI 125211) is a potent and selective antagonist of histamine H2-receptor (pA₂=7.3-7.8 for guinea-pig right atrium). Tiotidine has low affinity for both the H1 and the H3 receptors.

Irdabisant (CEP-26401) is a selective, orally active and blood-brain barrier (BBB) penetrant histamine H3 receptor (H3R) inverse agonist/inverse agonist with K_i values of 7.2 nM and 2.0 nM for rat H3R and human H3R, respectively. Irdabisant has relatively low inhibitory activity against hERG current with an IC₅₀ of 13.8 μM. Irdabisant has cognition-enhancing and wake-promoting activities in the rat social recognition model. Irdabisant can be used to research schizophrenia or cognitive impairment.

Bavisant (JNJ31001074AAC) dihydrochloride hydrate is an orally active, potent, brain-penetrating and highly selective antagonist of the histamine H₃ receptor. Bavisant dihydrochloride hydrate can be used for attention-deficit hyperactivity disorder (ADHD) research.

S 38093 is a brain-penetrant, orally active antagonist of H3 receptor, with K_is of 8.8, 1.44 and 1.2 μM for rat, mouse and human H3 receptors, respectively.

JNJ10191584 (VUF6002) is an orally active and selective histamine H₄ receptor antagonist with a K_i value of 26 nM. JNJ10191584 shows 540-fold selectivity to H₄ receptor over H₃ receptor with a K_i value of 14.1 μM. JNJ10191584 inhibits chemotaxis of eosinophils and mast cells with IC₅₀ values of 530 nM and 138 nM, respectively.

Thioperamide maleate (MR-12842 maleate) is a potent, orally available, brain penetrant and selective H3 receptor antagonist with a K_i of 4.3 nM for inhibition of [³H]histamine release. Thioperamide maleate inhibits [³H]histamine synthesis with a K_i of 31 nM.

PF-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).

Carcinine (β-Alanylhistamine) dihydrochloride is the dihydrochloride salt of Carcinine (HY-107567). Carcinine is a selective and orally active histamine H3 receptor antagonist with a K_i 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.

Proxyfan is a potent histamine H3 receptor antagonist with K_i 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.