-
Pharmatherapeutica 1983A double-blind, randomized study was carried out in 38 adult patients with non-infectious conjunctivitis to compare the efficacy and tolerance of oxymetazoline (0.025%)... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A double-blind, randomized study was carried out in 38 adult patients with non-infectious conjunctivitis to compare the efficacy and tolerance of oxymetazoline (0.025%) ophthalmic solution with that of naphazoline (0.04%) solution. Treatment was continued for 7 to 8 days and severity of symptoms was recorded before, during and at the end of therapy. At the end of the study period, 11 (69%) of 16 patients treated with oxymetazoline demonstrated a good to excellent response to therapy compared with 8 (53%) of 15 patients in the naphazoline-treated group. A statistically significant difference favouring oxymetazoline was observed in duration of action and the mean number of applications needed. No adverse reactions were reported in either treatment group.
Topics: Adult; Aged; Clinical Trials as Topic; Conjunctivitis; Double-Blind Method; Female; Humans; Imidazoles; Male; Middle Aged; Naphazoline; Ophthalmic Solutions; Oxymetazoline
PubMed: 6353428
DOI: No ID Found -
Topically applied oxymetazoline. Ocular vasoconstrictive activity, pharmacokinetics, and metabolism.Archives of Ophthalmology (Chicago,... Jul 1983Two double-blind, random-assignment clinical trials demonstrated the effectiveness of topical oxymetazoline hydrochloride in reducing histamine-induced hyperemia.... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Two double-blind, random-assignment clinical trials demonstrated the effectiveness of topical oxymetazoline hydrochloride in reducing histamine-induced hyperemia. Oxymetazoline hydrochloride at an optimum strength of 0.025% produced a marked and prolonged reduction of hyperemia, with the onset of effect occurring within one to five minutes of instillation. Safety indicators, including BP, heart rate, intraocular pressure, pupil size, and visual acuity, did not change significantly from baseline values. Oxymetazoline was absorbed slowly into the eye: only 0.006% of the original drug concentration was found in the aqueous humors of rabbits 30 minutes after instillation; the balance remained primarily in external ocular tissues. Metabolic studies in rabbits indicated that excreted amounts of unmetabolized radioactive oxymetazoline in urine following drug administration were similar (23%) for the ocular and nasal routes of application. The proportions of oxymetazoline metabolite to unchanged oxymetazoline were constant for all administration routes tested.
Topics: Administration, Topical; Adult; Animals; Clinical Trials as Topic; Conjunctivitis; Dose-Response Relationship, Drug; Double-Blind Method; Eye; Female; Hemodynamics; Humans; Hyperemia; Imidazoles; Intraocular Pressure; Male; Middle Aged; Oxymetazoline; Rabbits; Random Allocation; Visual Acuity
PubMed: 6347152
DOI: 10.1001/archopht.1983.01040020124022 -
Journal of Pharmacological Sciences Jul 2009The nasal decongestant oxymetazoline (OMZ) exhibits anti-oxidative and anti-inflammatory properties (I. Beck-Speier et al., J Pharmacol Exp Ther. 2006;316:842-851). In a...
The nasal decongestant oxymetazoline (OMZ) exhibits anti-oxidative and anti-inflammatory properties (I. Beck-Speier et al., J Pharmacol Exp Ther. 2006;316:842-851). In a follow up study, we hypothesized that OMZ generates pro-resolving lipoxins being paralleled by production of immune-modulating prostaglandin E(2) (PGE(2)) and anti-inflammatory 15(S)-hydroxy-eicosatetraenoic acid [15(S)-HETE] and depletion of pro-inflammatory leukotriene B(4) (LTB(4)). Human neutrophils (PMN) were chosen as the cellular system. The effect of OMZ on these parameters as well as on respiratory burst activity and oxidative stress marker 8-isprostane was analyzed in unstimulated and co-stimulated PMN by ultrafine carbon particles (UCP) or opsonized zymosan (OZ), respectively. In unstimulated cells, OMZ induced formation of PGE(2), 15(S)-HETE, and LXA(4). The levels of LTB(4) and 8-isoprostane were not affected, whereas respiratory burst activity was drastically inhibited. In UCP- and OZ-stimulated control cells, all parameters were elevated. Here, OMZ maintained the increased levels of PGE(2), 15(S)-HETE, and LXA(4), but substantially suppressed levels of LTB(4) and 8-isoprostane and inhibited the respiratory burst activity. These findings suggest a switch from the pro-inflammatory eicosanoid class LTB(4) to the pro-resolving LXA(4). Since LXA(4) is most relevant in returning inflamed tissue to homeostasis, OMZ is postulated to terminate rhinitis-related inflammation, thus contributing to shortening of disease duration.
Topics: Carbon; Cell Survival; Dinoprost; Eicosanoids; Humans; In Vitro Techniques; Lipoxins; Nasal Decongestants; Neutrophils; Oxymetazoline; Respiratory Burst; Zymosan
PubMed: 19609065
DOI: 10.1254/jphs.09012fp -
European Archives of... Jun 2008Oxymetazoline is often used as a decongestant in rhinitis patients who are suffering from nasal obstruction. It is used as a nasal drop or spray solution. The effect on... (Comparative Study)
Comparative Study
Oxymetazoline is often used as a decongestant in rhinitis patients who are suffering from nasal obstruction. It is used as a nasal drop or spray solution. The effect on nasal mucosa in vitro or in vivo is well known. However, the effect of the drug on tracheal smooth muscle has rarely been explored. During administration of the drug to the nose, it might affect the trachea via inhalation. We used our preparation to test the effectiveness of oxymetazoline on isolated rat's tracheal smooth muscle. A 5 mm long portion of rat trachea was submersed in 30 ml Kreb's solution in a muscle bath at 37 degrees C. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured using a transducer connected to a Pentium III computer equipped with polygraphy software. The following assessments were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10(-6)M methacholine as a parasympathetic mimetic; (3) effect of oxymetazoline on electrically induced tracheal smooth muscle contractions. Addition of parasympathetic mimetics to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of oxymetazoline induced a significant relaxation response when the preparation was up to 10(-4) M. At the same concentration, the drug also could inhibit EFS induced spike contraction. Oxymetazoline had negligible effect on the basal tension of trachea as the concentration increased. The degree of drug-induced tracheal contraction or relaxation was dose-dependent. The study indicated that high concentrations of oxymetazoline might actually antagonize cholinergic receptors of the trachea.
Topics: Animals; Dose-Response Relationship, Drug; Muscle Contraction; Muscle, Smooth; Oxymetazoline; Rats; Sympathomimetics; Trachea
PubMed: 17978828
DOI: 10.1007/s00405-007-0509-4 -
Acta Poloniae Pharmaceutica 2002The kinetics of the hydrolysis reaction of oxymetazoline hydrochloride in aqueous solution at three temperatures (343 K, 353 K, 363 K), over the pH-range 0.5-12.5 and...
The kinetics of the hydrolysis reaction of oxymetazoline hydrochloride in aqueous solution at three temperatures (343 K, 353 K, 363 K), over the pH-range 0.5-12.5 and ionic strength 0.5 has been investigated. The changes of concentration of oxymetazoline hydrochloride were followed by the HPLC method with UV detection. In the pH range from 0.45 to 12.50, the hydrolysis of oxymetazoline consists of hydrolysis of oxymetazoline molecules catalyzed by hydrogen ions, spontaneous hydrolysis of the dissociated and undissociated oxymetazoline molecules. A minimal rate of the hydrolysis oxymetazoline was observed to occur in the pH range from 2.0 to 5.0. Thermodynamic parameters of the reaction: energy, entropy and enthalpy of activation and the frequency factor for the specific rate constants were determined.
Topics: Drug Stability; Nasal Decongestants; Oxymetazoline; Pharmaceutical Solutions; Water
PubMed: 12026107
DOI: No ID Found -
Rhinology Sep 2003Topical decongestants are available over the counter and provide rapid relief of nasal obstruction for conditions of short duration, for example the common cold.... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Topical decongestants are available over the counter and provide rapid relief of nasal obstruction for conditions of short duration, for example the common cold. Manufacturers' recommendations are that topical decongestants should not be used regularly for more than 1 week in view of the risk of rebound mucosal hyperaemia with persistent nasal obstruction and refractoriness to further effects of decongestants. For this reason we performed a randomised double-blind placebo-controlled trial in 30 normal adult subjects with 0.05% oxymetazoline nasal spray 2 sprays (0.1 ml/spray) to each nostril 3 times daily over an extended period of 4 weeks. Degree of nasal blockage was assessed before and after 4 weeks treatment and for 2 weeks following discontinuation of treatment. Outcome measures included diary symptom scores and measurements of nasal peak inspiratory flow, airway resistance (using posterior active rhinomanometry) and volume (using acoustic rhinometry). Nasal patency was assessed at baseline and 15 minutes after oxymetazoline challenge at each clinic visit. Results demonstrated no significant increases in subjective nasal blockage throughout the 6 weeks study period in either oxymetazoline- or placebo-treated subjects. No significant differences were observed between groups for baseline measurements of nasal peak inspiratory flow, airway resistance or volume at each clinic visit. A highly significant decongestant effect of oxymetazoline was observed at each clinic visit with changes in all 3 measurements for both treatment groups, again with no significant differences between groups. In summary, in normal subjects, we identified no significant nasal blockage or impaired decongestant response to oxymetazoline following 4 weeks treatment with oxymetazoline compared to matched placebo nasal spray.
Topics: Administration, Intranasal; Adolescent; Adult; Diagnostic Techniques, Respiratory System; Double-Blind Method; Female; Humans; Male; Middle Aged; Nasal Decongestants; Nasal Obstruction; Oxymetazoline; Tachyphylaxis; Treatment Outcome
PubMed: 14579657
DOI: No ID Found -
Drug Metabolism and Disposition: the... Apr 2011Oxymetazoline (6-tert-butyl-3-(2-imidazolin-2-ylmethyl)-2,4-dimethylphenol) has been widely used as a nonprescription nasal vasoconstrictor for >40 years; however, its...
Oxymetazoline (6-tert-butyl-3-(2-imidazolin-2-ylmethyl)-2,4-dimethylphenol) has been widely used as a nonprescription nasal vasoconstrictor for >40 years; however, its metabolic pathway has not been investigated. This study describes the in vitro metabolism of oxymetazoline in human, rat, and rabbit liver postmitochondrial supernatant fraction from homogenized tissue (S9) fractions and their microsomes supplemented with NADPH. The metabolites of oxymetazoline identified by liquid chromatography (LC)/UV/tandem mass spectrometry (MS/MS), included M1 (monohydroxylation of the t-butyl group), M2 (oxidative dehydrogenation of the imidazoline to an imidazole moiety), M3 (monohydroxylation of M2), M4 (dihydroxylation of oxymetazoline), and M5 (dihydroxylation of M2). Screening with nine human expressed cytochromes P450 (P450s) identified CYP2C19 as the single P450 isoform catalyzing the formation of M1, M2, and M3. Glutathione conjugates of oxymetazoline (M6) and M2 (M7) were identified in the liver S9 fractions, indicating the capability of oxymetazoline to undergo bioactivation to reactive intermediate species. M6 and M7 were not detected in those liver S9 incubations without NADPH. Cysteine conjugates (M8 and M9) derived from glutathione conjugates and hydroxylated glutathione conjugates (M10 and M11) were also identified. The reactive intermediate of oxymetazoline was trapped with glutathione and N-acetyl cysteine and identified by LC/MS/MS. M6 was isolated and identified by one-dimensional or two-dimensional NMR as the glutathione conjugate of a p-quinone methide. We have shown the tendency of oxymetazoline to form p-quinone methide species via a bioactivation mechanism involving a CYP2C19-catalyzed two-electron oxidation. Nevertheless, we conclude that the formation of this reactive species might not be a safety concern for oxymetazoline nasal products because of the typical low-dose and brief dosage regimen limited to nasal delivery.
Topics: Acetylcysteine; Animals; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C19; Cytochrome P-450 Enzyme System; Glutathione; Humans; Hydroxylation; In Vitro Techniques; Indolequinones; Liver; Male; Microsomes, Liver; NADP; Oxidation-Reduction; Oxymetazoline; Rabbits; Rats; Sympathomimetics
PubMed: 21177487
DOI: 10.1124/dmd.110.036004 -
Molecular Pharmacology Jul 1988The nonselective alpha-adrenergic agonist oxymetazoline inhibits parathyroid hormone (PTH)-stimulated cAMP production in intact OK cells, an epithelial cell line derived...
The nonselective alpha-adrenergic agonist oxymetazoline inhibits parathyroid hormone (PTH)-stimulated cAMP production in intact OK cells, an epithelial cell line derived from an American opossum kidney. This inhibition, however, is not blocked by alpha 2-adrenergic receptor antagonists. After excluding several alternate hypotheses to explain this anomalous activity of oxymetazoline, we hypothesized that oxymetazoline activates a receptor in OK cells that is negatively coupled to adenylate cyclase but distinct from the alpha 2-adrenergic receptor. Prior exposure of OK cells to pertussis toxin blocks the inhibitory response to oxymetazoline, suggesting involvement of a guanine nucleotide-binding regulatory protein. Screening various compounds for attenuation of PTH-stimulated adenylate cyclase showed that serotonin (5HT) is a potent and fully efficacious agonist. Desensitization of alpha 2-receptor-mediated inhibition of cAMP production by epinephrine did not alter the response to either 5HT or oxymetazoline, indicating that these compounds do not produce their effect by activating alpha 2-adrenergic receptors. The 5HT1 receptor-selective antagonist methiothepin, but not ketanserin (5HT2-selective) or ICS-205,930 (5HT3-selective), blocked the response to both 5HT and oxymetazoline. The potency of methiothepin for antagonizing oxymetazoline-induced inhibition of PTH-stimulated cAMP production was not significantly different from its potency for the 5HT-induced effect. These data indicate that OK cells express a 5HT1 receptor that is negatively coupled to adenylate cyclase and that oxymetazoline is an agonist at these receptors.
Topics: Adenylyl Cyclase Inhibitors; Binding Sites; Cell Line; Cyclic AMP; Imidazoles; Kidney; Methiothepin; Oxymetazoline; Parathyroid Hormone; Receptors, Adrenergic, alpha; Receptors, Serotonin
PubMed: 2839761
DOI: No ID Found -
Fundamental & Clinical Pharmacology Dec 2010Oxymetazoline and xylometazoline are both used as nasal mucosa decongesting α-adrenoceptor agonists during a common cold. However, it is largely unknown which of the... (Comparative Study)
Comparative Study
Oxymetazoline and xylometazoline are both used as nasal mucosa decongesting α-adrenoceptor agonists during a common cold. However, it is largely unknown which of the six α-adrenoceptor subtypes are actually present in human nasal mucosa, which are activated by the two alpha-adrenoceptor agonists and to what extent. Therefore, mRNA expression in human nasal mucosa of the six α-adrenoceptor subtypes was studied. Furthermore, the affinity and potency of the imidazolines oxymetazoline and xylometazoline at these α-adrenoceptor subtypes were examined in transfected HEK293 cells. The rank order of mRNA levels of α-adrenoceptor subtypes in human nasal mucosa was: α(2A) > α(1A) ≥ α(2B) > α(1D) ≥ α(2C) >> α(1B) . Oxymetazoline and xylometazoline exhibited in radioligand competition studies higher affinities than the catecholamines adrenaline and noradrenaline at most α-adrenoceptor subtypes. Compared to xylometazoline, oxymetazoline exhibited a significantly higher affinity at α(1A) - but a lower affinity at α(2B) -adrenoceptors. In functional studies in which adrenoceptor-mediated Ca(2+) signals were measured, both, oxymetazoline and xylometazoline behaved at α(2B) -adrenoceptors as full agonists but oxymetazoline was significantly more potent than xylometazoline. Furthermore, oxymetazoline was also a partial agonist at α(1A) -adrenoceptors; however, its potency was relatively low and it was much lower than its affinity. The higher potency at α(2B) -adrenoceptors, i.e. at receptors highly expressed at the mRNA level in human nasal mucosa, could eventually explain why in nasal decongestants oxymetazoline can be used in lower concentrations than xylometazoline.
Topics: Adrenergic alpha-Agonists; Adult; Binding, Competitive; Female; HEK293 Cells; Humans; Imidazoles; Male; Nasal Mucosa; Oxymetazoline; RNA, Messenger; Receptors, Adrenergic, alpha
PubMed: 20030735
DOI: 10.1111/j.1472-8206.2009.00805.x -
General Dentistry 2017
Topics: Administration, Intranasal; Anesthesia, Dental; Anesthesia, Local; Dental Restoration, Permanent; Humans; Maxillary Nerve; Nasal Sprays; Oxymetazoline; Tetracaine
PubMed: 28253176
DOI: No ID Found