nasal

Quazolast (RHC 3988) is a potent mediator release inhibitor and is a control against ragweed antigenic nasal challenge. quazolast is superior to placebo in preventing nasal congestion and nasal itching following ragweed nasal challenge.

Fexofenadine (Carboxyterfenadine), an antihistamine pharmaceutical drug, is used to treat allergy symptoms, such as nasal congestion, hay fever, and urticaria. Compared to first-generation antihistamines, Fexofenadine is less able to pass the blood-brain barrier and cause sedation.

mTOR/HDAC-IN-1 (Compound 50) is a dual inhibitor targeting both mTOR and HDAC with respective IC50 values of 0.49 nM and 0.91 nM. It holds potential as an anti-cancer agent [1].This compound is unstable in powder form and other related salt forms are recommended.

5-A-RU (5-Amino-6-(D-ribitylamino)uracil), a precursor of bacterial Riboflavin, is a mucosal-associated invariant T (MAIT) cells activator. 5-A-RU forms potent MAIT-activating antigens via non-enzymatic reactions with small molecules that are derived from other metabolic pathways.This compound is unstable in powder form and other related salt forms are recommended.

Bencycloquidium Bromide is a muscarinic M3 antagonist. Bencycloquidium bromide inhibits nasal hypersecretion in a rat model of allergic rhinitis. Bencycloquidium Bromide showed high affinity toward the M(3) receptor in Chinese hamster ovary (CHO) cells (M(1) pKi=7.86, M(2) pKi=7.21, M(3) pKi=8.21); pA(2)=8.85, 8.71 and 8.57 in methacholine-induced contraction of trachea, ileum and urinary bladder, 8.19 in methacholine-induced bradycardia of right atrium in vitro, respectively.This compound is unstable in powder form and other related salt forms are recommended.

14,15-Leukotriene D4 (14,15-LTD4) is a member of an alternate class of LTs synthesized by a pathway involving the dual actions of 15- and 12-lipoxygenases (15- and 12-LOs) on arachidonic acid via 15-HpETE and 14,15-LTA4 intermediates. 14,15-LTD4 is classified as an eoxin (EXD4), because it is formed mostly by eosinophils. However, mast cells and nasal polyps can synthesize 14,15-LTD4 as well. Little is known about the physiological actions of 14,15-LTD4. It has weak contractile activity on both guinea pig ileum and pulmonary parenchyma in contrast to the effects of 5-LO-derived LTs. However, in an in vitro permeability assay, 14,15-LTD4 can increase vascular permeability of human endothelial cell monolayers, with similar potency to that of 5-LO-derived LTs, resulting in plasma leakage, a hallmark of inflammation.

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg/ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g/animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

Leukotrienes (LTs) are a group of acute inflammatory mediators derived from arachidonic acid in leukocytes. The majority of these metabolites are formed through the 5-lipoxygenase (5-LO) pathway. 14,15-LTE4 is a metabolite of 14,15-LTC4 and 14,15-LTD4, an alternate class of LTs synthesized by a pathway involving the dual actions of 15- and 12-LOs on arachidonic acid via 15-HpETE and 14,15-LTA4 intermediates. These metabolites are classified as eoxins because they are formed mostly by eosinophils. Mast cells and nasal polyps can synthesize 14,15-LTC4 as well, however metabolism to 14,15-LTE4 in these cells and tissue has not been documented. 14,15-LTE4 increases vascular permeability of human endothelial cell monolayers with about 10-fold less potency than LTC4, but approximately 100-fold greater potency than histamine.

Lugdunin is an antibiotic peptide that disrupts membrane potential in bacteria, demonstrating activity against Gram-positive species including S. aureus, and effectively reducing skin and nasal colonization of this pathogen. Moreover, Lugdunin stimulates the production of LL-37 and CXCL8/MIP-2 in human keratinocytes and mouse skin [1].

Tetrahydrozoline hydrochloride (Murine Plus) is an imidazoline derivative with alpha receptor agonist activity.

Clonazoline is a coronary vasodilator that is an imidazoline sympathomimetic, an alpha-adrenoreceptor agonist. It was used as a nasal decongestant and vasoconstrictor.

Cetylpyridinium chloride monohydrate (Hexadecylpyridinium chloride monohydrate) , a cationic quaternary ammonium compound, is used in certain classes of throat sprays, mouthwashes, lozenges, toothpaste, nasal sprays, and breath sprays. Cetylpyridinium chloride monohydrate has also been used as an ingredient in certain pesticides. It is an antiseptic with killing bacteria and other microorganisms. It can be potent in reducing gingivitis and preventing dental plaque. It may result in brown stains between the teeth and on the surface of teeth.

Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids that can be easily absorbed in the small intestine[1]. Pepsin is stable at pH ranges as high as pH 6. Above this pH, pepsin is rapidly irreversibly inactivated and elevation of pH of the reaction mixture to pH 8 results in complete inactivation of pepsin[2]. Pepsin has been posited to be a reliable biological marker of EER. An immunologic pepsin assay of combined sputum and saliva was determined to be 100% sensitive and 89% specific for detection of EER (based on pH-metry), and an enzymatic test of nasal lavage fluid (100% sensitivity and 92.5% specificity) demonstrated an increased incidence of EER in patients with chronic rhinosinusitis[3]. Cultured hypopharyngeal epithelial (FaDu) cells were exposed to human pepsin (0.1 mg/mL) at pH 7.4 for either 1 hour or 12 hours at 37°C and both mitochondria and Golgi complexes were clearly damaged. This finding reveals a novel mechanism by which pepsin could cause cell damage, potentially even in nonacidic refluxate[4].

TAS 205 is an inhibitor of hematopoietic prostaglandin D synthase (H-PGDS; IC50= 55.8 nM).1It is selective for H-PGDS over lipocalin-type PGDS (L-PGDS) at 100 μM, as well as over enzyme and receptor panels at 10 μM. TAS 205 inhibits production of prostaglandin D2induced by A23187 in KU812 human and RBL-2H3 rat basophils with IC50values of 78.3 and 181.3 nM, respectively. It inhibits ovalbumin-induced nasal lavage fluid eosinophil infiltration and late-phase nasal obstruction in an ovalbumin-sensitized guinea pig model of allergic rhinitis when administered at a dose of 30 mg/kg. 1.Aoyagi, H., Kajiwara, D., Tsunekuni, K., et al.Potential synergistic effects of novel hematopoietic prostaglandin D synthase inhibitor TAS-205 and different types of anti-allergic medicine on nasal obstruction in a Guinea pig model of experimental allergic rhinitisEur. J. Pharmacol.875173030(2020)

Sodium salicylate (2-Hydroxybenzoic acid sodium salt), a metabolite of acetylsalicylic acid, can inhibit NF-kB and reduce oxidative stress.

1. Prunetin (Prunusetin) significantly reduces serum levels of inflammatory cytokines and mortality in mice challenged with lipopolysaccharide. 2. Prunetin mediates anti-obesity/adipogenesis effects by suppressing obesity-related transcription through a feedback mechanism that regulates the expression of adiponectin, adipoR1, adipoR2, and AMPK. 3. Prunetin and biochanin A are potent reducers of NF-κB and ERK activation, zonula occludens 1 tyrosine phosphorylation, and metalloproteinase-mediated shedding activity, which may account for the barrier-improving ability of these isoflavones. 4. Prunetin significantly suppresses ATP-induced mucin secretion from cultured RTSE cells; Prunetin inhibits the production of MUC5AC mucin protein induced by EGF or PMA from NCI-H292 cells; Prunetin also inhibits the expression of MUC5AC mucin gene induced by EGF or PMA from NCI-H292 cells.

Povafonidine (PGE-6201204) is a potent alpha-2 adrenoreceptor agonist. Povafonidine can constrict blood vessels and reduce mucosal congestion which can be used for nasal congestion research [1].

Leukotriene C4 (14,15-LTC4) is an inflammatory mediator synthesized from arachidonic acid through the actions of 15- and 12-lipoxygenases (LOs), involving intermediates such as 15-HpETE and 14,15-LTA4. Unlike the majority of leukotrienes formed via the 5-LO pathway, 14,15-LTC4 is an eoxin predominantly produced by eosinophils, although mast cells and nasal polyps can also synthesize it. While its physiological roles are not well understood, 14,15-LTC4 exhibits limited contractile activity on guinea pig ileum and pulmonary parenchyma. However, it can increase vascular permeability in human endothelial cell monolayers in vitro with potency comparable to 5-LO-derived leukotrienes, contributing to plasma leakage characteristic of inflammation.

2′-Deoxy-2′-fluoroguanosine is a nucleoside analog that potently inhibits influenza virus A and B strains(EC90 <0.35 μM). 2'-Deoxy-2'-fluoroguanosine is an inhibitor of influenza virus replication in the upper respiratory tract, improving fever and nasal inflammation.

N’-Nitrosonornicotine is a tobacco-specific N-nitrosamine and carcinogen that has been found in unburned tobacco and cigarette smoke.1It induces the formation of DNA adducts in isolated rat nasal mucosa and esophagus. N’-Nitrosonornicotine induces tumor formation in rat esophagus and nasal cavity, mouse lung, forestomach, and trachea, and hamster trachea and forebrain. Urinary levels of N’-nitrosonornicotine are positively correlated with the risk of esophageal cancer in smokers.2 1.Hecht, S.S.Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosaminesChem. Res. Toxicol.11(6)559-603(1998) 2.Yuan, J.-M., Knezevich, A.D., Wang, R., et al.Urinary levels of the tobacco-specific carcinogen N’-nitrosonornicotine and its glucuronide are strongly associated with esophageal cancer risk in smokersCarcinogenesis32(9)1366-1371(2011)

Tetrahydrozoline (Tetryzoline) nitrate is a derivative of imidazoline. It is an α-adrenergic agonist that causes vasoconstriction. Tetrahydrozoline is widely used for the nasal congestion and conjunctival congestion research [1] [2].

(-)-Fargesol is a nartural product from the flowers buds of Magnolia fargesii,the dried flower buds of M. fargesii, has been used as therapy for nasal empyema and headache.

Highly potent and selective MMP13 inhibitor (IC50 = 6.9 pM). Exhibits >2600-fold selectivity for MMP13 over related MMPs. Inhibits degradation of bovine nasal septum cartilage explants in vitro . Orally bioavailable. Nara et al (2014) Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1 binding site. Bioorg.Med.Chem. 22 5487 PMID:25192810

Mebhydrolin napadisylate (Incidal) is an antihistamine used to relieve allergic symptoms caused by histamine release, including nasal allergies and allergic dermatosis.

Epimagnolin A is a lignan obtained from the flower buds of Magnolia fargesii, which is traditionally used in Asian medicine for treating headache and nasal congestion.

Uridine-5'-O-(3-thiotriphosphate) (UTP-γ-S) is a hydrolysis-resistant UTP derivative and an agonist of the purinergic P2Y2 receptor. It effectively induces inositol phosphate formation in 1321N1 astrocytoma cells harboring the human P2Y2 receptor (EC50 = 240 nM) and stimulates chloride secretion in a dose-dependent manner in primary nasal epithelial cells from cystic fibrosis patients. Moreover, UTP-γ-S prompts vasoconstriction in isolated human coronary arteries (EC50 = 25.1 µM).

OxyMetazoline is an α-adrenoceptor agonist that acts on α1A (IC50: 0.02 μM), α1B (IC50: 0.25 μM), α2A (IC50: 0.58 μM) and α2C (IC50: 0.13 μM). OxyMetazoline can be used in studies to relieve nasal mucosal congestion.

Laninamivir trifluoroacetate is an antiviral compound that is a drug used for the treatment and prophylaxis of Influenzavirus A and Influenzavirus B. It is a long-acting neuraminidase inhibitor administered by nasal inhalation.

Cafaminol (methylcoffanolamine) is a vasoconstrictor and anticatarrhal of the methylxanthine family related to caffeine which is used as a nasal decongestant.

3M-011, a potent dual toll-like receptor TLR7/8 agonist and cytokine inducer, serves as a powerful adjuvant to radiotherapy, eliciting significant local and systemic immune responses. Additionally, it effectively inhibits H3N2 influenza viral replication in the nasal cavity and exhibits strong antitumor activity[1][2][3].

Synephrine (Oxedrine) is sympathetic alpha-adrenergic agonist used as a vasoconstrictor in circulatory failure, asthma, nasal congestion, and glaucoma.

ARC 239 dihydrochloride is a selective α2B adrenoceptor antagonist (pKD values are 8.8, 6.7 and 6.4 at α2B, α2A, and α2D receptors respectively).

Voxvoganan (LTX-109) trihydrochloride, a topical antimicrobial, demonstrates a high efficacy against S. aureus, exhibiting a MIC range of 2 to 4 μg/mL. It is utilized in research for treating bacterial skin infections, fungal infections, and nasal decolonization of MRSA [1] [2].

Nafarelin is a gonadotropin-releasing hormone agonist (GnRH agonist) which acts as an analog of GnRH. Nafarelin increases the release of FSH and LH by the anterior pituitary, which in turn leads to an increase of estrogen/progesterone. When administered, Nafarelin has the purpose of causing increase estrogen that will negatively feed back upon hypothalamus to decrease GnRH ( negative feedback loop ) Through negative feedback, Nafarelin causes a decrease in pituitary secretion of gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH). Nafarelin may be used in the treatment of estrogen-dependent conditions (such as endometriosis or uterine fibroids), to treat central precocious puberty, and to control ovarian stimulation in IVF. It is normally delivered via a nasal spray. Nafarelin acetate is marketed by Searle (now part of Pfizer) under the brand name Synarel.

Lerimazoline(Trimazoline, Trimizoline, ST-71) is used in the form of tramazoline hydrochloride in nasal decongestant preparations. It is used to inhibits the secretion of nasal mucus as an α-adrenergic receptor agonist.

L-Phenylephrine is an alpha-adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.

Tetrahydrozoline (Tetryzoline), an alpha agonist, have an effect on the constriction of conjunctival blood vessels. This contributes to relieve the redness of the eye resulted from minor ocular irritants.

Tramazoline hydrochloride is commonly used in nasal spray as a nasal decongestant by acting as an α-adrenergic receptor agonist that inhibits secretion of nasal mucus.

AVX 13616, Avexa's leading antibacterial candidate, demonstrates significant in vivo antibacterial efficacy, especially against drug-resistant Staphylococcus pathogens, with an IC50 value of 2-4 µg/ml (MICs) and is targeted as an antibacterial agent. Comparable in activity to mupirocin within a nasal decolonization model, AVX13616 necessitated only a single application for effectiveness. This compound, alongside others, exhibited broad-spectrum antibacterial action, achieving MICs of 2-4 micrograms per milliliter against various isolates, including S. aureus, coagulase-negative staphylococci, enterococci, MRSA, VISA, and VRSA. Aimed for topical use and the treatment of wound infection or catheter-related infections, a solitary 5% (w/w) AVX13616 application (roughly equivalent to 2% mupirocin) proved as efficacious as twice-daily 2% mupirocin over five days in decolonizing MRSA in mice.

Thonzylamine (neohetramine) is an antihistamine and anticholinergic drug. It is available as combination products with Clofedanol or Phenylephrine for temporary relief of symptoms of common cold, hay fever (allergic rhinitis) or other upper respiratory allergies.

Xylometazoline hydrochloride (Xylometazoline HCl) is an α-adrenoceptor agonist usually used as nasal decongestant.

Fluticasone furoate (Avamys) is a synthetic trifluorinated corticosteroid derived from fluticasone with a Kd of 0.3 nM. Fluticasone furoate has potent anti-inflammatory, anti-asthmatic activity, and low systemic exposure. Fluticasone furoate can be used as a nasal spray for studies about allergic rhinitis treatment.

Clonazoline HCl is the salt form of Clonazoline, a coronary vasodilator that is an imidazoline sympathomimetic, an alpha-adrenoreceptor agonist. It was used as a nasal decongestant and vasoconstrictor.

N-Nitrosodiethylamine (NDEA) is a potent hepatocarcinogenic dialkylnitrosoamine. N-Nitrosodiethylamine is mainly present in water, tobacco smoke, cheddar cheese, cured, fried meals and many alcoholic beverages. N-Nitrosodiethylamine is responsible for the changes in the nuclear enzymes associated with DNA repair/replication. N-Nitrosodiethylamine results in various tumors in all animal species. The main target organs are the liver, nasal cavity, trachea, lung and esophagus.

N-Nitrosodiethylamine-d10 is a deuterated compound of N-Nitrosodiethylamine. N-Nitrosodiethylamine has a CAS number of 55-18-5. N-Nitrosodiethylamine is a potent hepatocarcinogenic dialkylnitrosoamine. N-Nitrosodiethylamine is mainly present in water, tobacco smoke, cheddar cheese, cured, fried meals and many alcoholic beverages. N-Nitrosodiethylamine is responsible for the changes in the nuclear enzymes associated with DNA repair/replication. N-Nitrosodiethylamine results in various tumors in all animal species. The main target organs are the liver, nasal cavity, trachea, lung and esophagus.

Fluticasone Furoate-d3 is a deuterated compound of Fluticasone Furoate. Fluticasone Furoate has a CAS number of 397864-44-7. Fluticasone furoate is a synthetic trifluorinated corticosteroid derived from fluticasone with a Kd of 0.3 nM. Fluticasone furoate has potent anti-inflammatory, anti-asthmatic activity, and low systemic exposure. Fluticasone furoate can be used as a nasal spray for studies about allergic rhinitis treatment.