5-HT Receptor Inhibitor

Ebelin lactone is an acetylcholinesterase (AChE) inhibitor, with a K_i of 0.45 μM against human M1 muscarinic acetylcholine receptor (mAChR) and a K_i of 4.21 μM against human 5-HT2A serotonin receptor. Ebelin lactone binds to the allosteric cavity above the orthosteric site of M1 via nonpolar interactions with subtype-selective residues. Ebelin lactone binds to the cavity between transmembrane helices 4 and 5 of 5-HT2A through nonpolar interactions with orthosteric site residues. Ebelin lactone exhibits free radical scavenging activity, inhibits cancer cell proliferation, and regulates memory and cognitive processes by interacting with M1 and 5-HT2A receptors. Ebelin lactone can be used in studies related to Alzheimer's disease, breast cancer and colorectal cancer.

Harmine is a natural dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) inhibitor with anticancer and anti-inflammatory activities. Harmine has a high affinity of 5-HT_2A serotonin receptor, with an K_i of 397 nM.

Risperidone is a serotonin 5-HT₂ receptor blocker, P-Glycoprotein inhibitor and potent dopamine D₂ receptor antagonist, with K_is of 4.8, 5.9 nM for 5-HT_2A and dopamine D₂ receptor, respectively.

Vortioxetine (Lu AA 21004) is an antagonist of 5-HT_3A and 5-HT₇ receptors (K_i: 3.7 nM, 19 nM) and an inhibitor of serotonin transporter (SERT) (K_i: 1.6 nM), as well as a 5-HT_1A agonist and a partial agonist of 5-HT_1B (K_i: 15 nM, 33 nM).

Paroxetine (BRL29060) is an orally active and selective serotonin reuptake inhibitor (SSRI) and apoptosis inducer with blood-brain barrier permeability. Paroxetine inhibits nitric oxide synthase and CYP2D6, induces desensitization of 5-HT1A/1B/1D autoreceptors, downregulates 5-HT2 receptors, and promotes the production of inflammatory cytokines. Paroxetine is a weak norepinephrine (NE) uptake inhibitor and possesses antitumor activity. Paroxetine is widely used in research concerning depression, obsessive-compulsive disorder, panic disorder, social phobia, generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, hot flashes, and related conditions.

Paroxetine (BRL29060) hydrochloride is an orally active and selective serotonin reuptake inhibitor (SSRI) and apoptosis inducer with blood-brain barrier permeability. Paroxetine hydrochloride inhibits nitric oxide synthase and CYP2D6, induces desensitization of 5-HT1A/1B/1D autoreceptors, downregulates 5-HT2 receptors, and promotes the production of inflammatory cytokines. Paroxetine hydrochloride is a weak norepinephrine (NE) uptake inhibitor and possesses antitumor activity. Paroxetine hydrochloride is widely used in research concerning depression, obsessive-compulsive disorder, panic disorder, social phobia, generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, hot flashes, and related conditions.

PCPA methyl ester hydrochloride (4-Chloro-DL-phenylalanine methyl ester hydrochloride), a reversible tryptophan hydroxylase inhibitor, is a serotonin (5-HT) synthesis inhibitor. PCPA methyl ester hydrochloride crosses the blood brain barrier and reduces 5-HT central availability.

Pimavanserin is a selective, brain-penetrant, inverse agonist of the 5-HT2A receptor with pIC₅₀ and pK_d of 8.73 and 9.3, respectively.

Vortioxetine (Lu AA 21004) hydrobromide is an antagonist of 5-HT_3A and 5-HT₇ receptors (K_i: 3.7 nM, 19 nM) and an inhibitor of 5-hydroxytryptamine transporter (SERT) (K_i: 1.6 nM), as well as a 5-HT_1A agonist and a partial 5-HT_1B agonist (K_i: 15 nM, 33 nM).

Nefazodone is an orally active phenylpiperazine antidepressant. Nefazodone can potently and selectively block postsynaptic 5-HT_2A receptors, and moderately inhibit 5-HT and noradrenaline reuptake. Nefazodone can also relieve the adverse effects of stress on the the immune system of mice. Nefazodone has a high affinity for CYP3A4 isoenzyme, which indicates that it has certain risk of agent-agent interaction.

Amitriptyline is an orally active tricyclic antidepressant (TCA). Amitriptyline 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 is also an agonist at α2A and TrkA/TrkB receptors, thereby exerting analgesic and neurotrophic activities (inhibiting cell apoptosis). Amitriptyline can reduce inflammation, angiogenesis and fibrosis. Amitriptyline binds to DAT (with K_i = 2.58 μM). Amitriptyline 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 can block sodium channels and hERG potassium channel (IC₅₀ = 4.78 μM) and it has cardiotoxicity.

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.

4-Chloro-L-phenylalanine (L-PCPA) is a tryptophan hydroxylase inhibitor targeting TPH1 and TPH2, with the activity of blocking serotonin biosynthesis. 4-Chloro-L-phenylalanine reduces the levels of serotonin and its metabolites in the brain without impairing the survival of serotonergic neurons. 4-Chloro-L-phenylalanine enhances anhedonic, depression-like and anxiety-like behaviors in mice with depleted noradrenergic and dopaminergic neurons. 4-Chloro-L-phenylalanine acts as a decarboxylation substrate for aromatic L-amino acid decarboxylase from Bacillus atrophaeus. 4-Chloro-L-phenylalanine can be used in studies related to Parkinson's disease.

Harmine Hydrochloride (Telepathine Hydrochloride) is a natural DYRK inhibitor with anticancer and anti-inflammatory activities. Harmine has a high affinity of 5-HT_2A serotonin receptor, with an K_i of 397 nM.

WAY-100635 maleate is a potent and selective 5-hydroxytryptamine 1A (5-HT1A) receptor antagonist with an IC₅₀ value of 0.91 nM and K_i value of 0.39 nM. WAY-100635 maleate has pIC₅₀ values for 5-HT1A and α1-adrenergic receptors of 8.9 and 6.6, respectively. WAY-100635 maleate is also a potent dopamine D₄ receptor agonist.

Jatrorrhizine chloride is an alkaloid isolated from Coptis chinensis with neuroprotective, antimicrobial, antiplasmodial and antioxidant activities. Jatrorrhizine chloride is a potent and orally active inhibitor of AChE (IC₅₀=872 nM) over >115-fold selectivity for BuChE. Jatrorrhizine chloride reduces uptake of serotonin (5-HT) and norepinephrine (NE) via inhibition of uptake-2 transporters.

Cyproheptadine acts as a p38 MAP kinase activator, CHK2 activator, histamine H1 receptor inhibitor and serotonin receptor inhibitor. Cyproheptadine mediates cell cycle arrest via G1 phase arrest, G1/S transition arrest, G0/G1 phase arrest, reduced expression of cyclins D1/D2/D3, upregulated expression of HBP1, p16, p21, p27, and decreased phosphorylation of retinoblastoma protein. Cyproheptadine induces Apoptosis by increasing PARP and cleaved PARP, as well as activating the mitochondrial caspase pathway. Cyproheptadine inhibits tumor growth with extremely low toxicity to normal cells. Cyproheptadine can be used in research related to hepatocellular carcinoma, multiple myeloma and acute myeloid leukemia.

Pimavanserin (ACP-103) hemitartrate is a potent and brain-penetrant5-HT 2A receptor inverse agonist with pIC₅₀ and pK_i of 8.73 and 9.3, respectively.

Cyproheptadine hydrochloride (Cyproheptadine HCl) acts as a p38 MAP kinase activator, CHK2 activator, histamine H1 receptor inhibitor and serotonin receptor inhibitor. Cyproheptadine hydrochloride mediates cell cycle arrest via G1 phase arrest, G1/S transition arrest, G0/G1 phase arrest, reduced expression of cyclins D1/D2/D3, upregulated expression of HBP1, p16, p21, p27, and decreased phosphorylation of retinoblastoma protein. Cyproheptadine hydrochloride induces Apoptosis by increasing PARP and cleaved PARP, as well as activating the mitochondrial caspase pathway. Cyproheptadine hydrochloride inhibits tumor growth with extremely low toxicity to normal cells. Cyproheptadine hydrochloride can be used in research related to hepatocellular carcinoma, multiple myeloma and acute myeloid leukemia.

Oxatomide (KW-4354) is an orally active dual antagonist of the H1-histamine receptor and the P2X7 receptor, as well as an inhibitor of serotonin. Oxatomide possesses antihistaminic, antiallergic and anti-inflammatory activities. Oxatomide can be used in the research of allergic diseases.