H₁ Receptor Antagonist

Clemastine (HS-592; Meclastine) fumarate is an orally active, blood-brain barrier-permeable H1 histamine receptor (H1 histamine receptor) antagonist with potent antiallergic effects. Clemastine fumarate also antagonizes muscarinic acetylcholine receptors (mAChR), particularly the M1 and M4 subtypes. In addition to antihistamine effects, Clemastine fumarate exhibits multiple pharmacological activities, especially in promoting central nervous system remyelination, activating autophagy and pyroptosis, exerting anti-apoptotic and neuroprotective effects, and suppressing inflammation .

Desloratadine (Sch34117) is an orally active and selective H1 receptor antagonist (K_i=0.9 nM) with anti-inflammatory and anti-allergic activities. Desloratadine inhibits the release of histamine and LTC4 from human basophils and targets the regulatory signals of IL-4 and IL-13 production in basophils. Desloratadine significantly alleviates SAR symptoms in patients with concurrent asthma and can be used in the study of seasonal allergic rhinitis and chronic idiopathic urticaria.

Astemizole (R 43512), a second-generation antihistamine agent to diminish allergic symptoms with a long duration of action, is a histamine H1-receptor antagonist, with an IC₅₀ of 4 nM. Astemizole also shows potent hERG K⁺ channel blocking activity with an IC₅₀ of 0.9 nM. Astemizole has antipruritic effects.

Terfenadine ((±)-Terfenadine) is a potent open-channel blocker of hERG with an IC₅₀ of 204 nM. Terfenadine, an H1 histamine receptor antagonist, acts as a potent apoptosis inducer in melanoma cells through modulation of Ca²⁺ homeostasis. Terfenadine induces ROS-dependent apoptosis, simultaneously activates Caspase-4, -2, -9.

Diphenhydramine is a first-generation histamine H1-receptor antagonist with anti-cholinergic effect. Diphenhydramine hydrochloride can across the ovine blood-brain barrier (BBB) .

Fexofenadine (MDL-16455) is an orally active and nonsedative H1 receptor antagonist. Fexofenadine can be used in allergic rhinitis and chronic idiopathic urticarial research.

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.

Ebastine (LAS-W 090) is an orally active, second-generation histamine H1 receptor antagonist. Ebastine can be used for the symptoms of allergic rhinitis and chronic idiopathic urticaria research.

Mirtazapine (Org3770) is a potent and orally active noradrenergic and specific serotonergic antidepressant (NaSSA) agent. Mirtazapine is also a 5-HT₂, 5-HT₃, histamine H1 receptor and α2-adrenoceptor antagonist with pK_i values of 8.05, 8.1, 9.3 and 6.95, respectively.

(S)-(+)-Dimethindene maleate, an enantiomer, is a potent M₂-selective muscarinic receptor antagonist (pA₂ = 7.86/7.74; pK_i = 7.78). (S)-(+)-Dimethindene maleate shows lower affinities for the muscarinic M₁ (pA₂ = 6.83/6.36; pK_i = 7.08), the M₃ (pA₂ = 6.92/6.96; pK_i = 6.70) and the M₄ receptors (pK_i = 7.00), respectively. (S)-(+)-Dimethindene maleate also is a histamine H₁ receptor antagonist (pA₂ = 7.48).

Diphenhydramine hydrochloride is a first-generation histamine H1-receptor antagonist with anti-cholinergic effect. Diphenhydramine hydrochloride can across the ovine blood-brain barrier (BBB).

Fexofenadine (MDL-16455) hydrochloride is an orally active and nonsedative H₁ receptor antagonist. Fexofenadine hydrochloride can be used in allergic rhinitis and chronic idiopathic urticarial research.

Meclizine (Meclozine) dihydrochloride, an antihistamine, reversibly inhibits the interaction of histamine at the H1 receptors. Meclizine dihydrochloride is a member of the piperazine class of H1 antagonists. Meclizine dihydrochloride is an effective anti-motion sickness agent. Meclizine dihydrochloride crosses the blood-brain barrier. Meclizine dihydrochloride can be used for the research of polyQ toxicity disorders, such as Huntington's disease. Meclizine dihydrochloride is an agonist ligand for mouse constitutive androstane receptor (CAR) and an inverse agonist for Human CAR.

Mepyramine maleate (Pyrilamine maleate) is a selective histamine H1 receptor antagonist and KCNQ channel inhibitor, with an IC₅₀ of 12.5 μM against KCNQ2/Q3. Mepyramine maleate shows no activity against allergic asthma in mice when used alone, but modulates the effect of JNJ 7777120 (HY-13508) on allergic asthma in mice; it inhibits the development of morphine physical dependence and increases histamine levels in mouse brains. Mepyramine maleate can be used in studies related to seizures, convulsions, allergic asthma and morphine physical dependence.

Cetirizine dihydrochloride, a second-generation antihistamine and the carboxylated metabolite of hydroxyzine, is a specific, orally active and long-acting histamine H1-receptor antagonist. Cetirizine dihydrochloride marks antiallergic properties and inhibits eosinophil chemotaxis during the allergic response.

Bepotastine is a selective and orally active second-generation histamine H1 receptor antagonist, can suppress the expression of nerve growth factor (NGF). Bepotastine has the potential for allergic rhinitis, allergic conjunctivitis and urticaria/pruritus research.

Epinastine (WAL801) is a selective and orally active histamine H1 receptor antagonist, CD96/PVR inhibitor and mast cell stabilizer. Epinastine has high affinity for neuronal octopamine receptors in locusts (K_i = 2 nM) and honeybees (K_i = 1.1 nM). Epinastine hydrochloride inhibits TARC, IL-8, and IL-4. Epinastine activates anti-colon cancer immunity and inhibits Substance P (HY-P0201)-induced scratching behavior and increased vascular permeability. Epinastine can be used in the research of allergic diseases.

Azelastine hydrochloridem, an antihistamine, is a potent and selective histamine 1 (H₁) antagonist. Azelastine hydrochloride can be used for the research of allergic rhinitis, asthma, diabetic hyperlipidemic and SARS-CoV-2.

Chlorpheniramine maleate is a histamine H1 receptor antagonist with an IC₅₀ of 12 nM.

Hydroxyzine dihydrochloride, a benzodiazepine antihistamine agent, acts as a orally active histamine H1-receptor and serotonin antagonist. Hydroxyzine dihydrochloride has anxiolytic effect and can be used forthe research of generalised anxiety disorder.