Disease relevance of oxymetazoline

• Bradycardia, hypotension, and near-syncope associated with Afrin (oxymetazoline) nasal spray [1].
• Effects of posture and oxymetazoline were similar in snorers with or without sleep apnea [2].
• The nasal decongestant oxymetazoline effectively reduces rhinitis symptoms [3].
• In intact anesthetized, vagotomized rats or in pithed rats with a submaximal tachycardia evoked by electrical stimulation of the spinal cord, clonidine and oxymetazoline, in contrast to cirazoline (5.0 micrograms/kg i.v.), decreased heart rate through excitation of alpha-2 adrenoceptors [4].
• We report a case of chronic use of nasal oxymetazoline associated with thunderclap headache due to reversible segmental intracranial vasoconstriction [5].

Psychiatry related information on oxymetazoline

• A case of panic disorder precipitated by oxymetazoline withdrawal [6].
• It is hypothesized that oxymetazoline needs to be applied locally to the area of the olfactory cleft in order to significantly improve olfaction during the course of the common cold [7].
• We conclude that oxymetazoline nose drops, commonly used in acute rhinitis and sinusitis, interfere with the normal defense mechanisms during bacterially induced sinusitis, possibly by a decrease in mucosal blood flow [8].

High impact information on oxymetazoline

• Similar increments (above basal) in the concentration of InsP(6) induced by oxymetazoline prevented AP-2 binding to the NKA alpha-subunit in response to dopamine [9].
• The effect of oxymetazoline on Na+,K(+)-ATPase activity was prevented by a specific peptide inhibitor of calcineurin, as well as by FK 506, an immunosuppressant agent known to inhibit calcineurin; these results indicate that the action of oxymetazoline is mediated via activation of calcineurin (a calcium/calmodulin-dependent protein phosphatase) [10].
• The alpha 1a-selective agonist oxymetazoline induced the co-internalization of the alpha 1a- and alpha 1b-AR, whereas the alpha 1b-AR could not co-internalize with the NK1 tachykinin or CCR5 chemokine receptors [11].
• In cerebral vessels, endothelial alpha2-adrenoceptor-dependent stimulation induced greater contractile responses in treated rats which were sensitive to bosentan, suggesting that oxymetazoline stimulates ET-1 release from the endothelium [12].
• Pretreatments with NPY (20 nmol), oxymetazoline hydrochloride (20 nmol), or saline solution (NaCl 0.9%) were administered in one nostril 5 minutes before nasal challenge with grass pollen allergen (10,000 standardized quality units) [13].

Chemical compound and disease context of oxymetazoline

• In conclusion, the long-term use of benzalkonium chloride in oxymetazoline nasal spray accentuates the severity of rhinitis medicamentosa in healthy volunteers [14].
• Using rhinostereometry, it has also been shown that the long-term use of the preservative benzalkonium chloride (BKC) in oxymetazoline nasal spray accentuates the severity of rhinitis medicamentosa in healthy volunteers [15].
• Subsequently, experiments have shown that moxonidine and oxymetazoline, but not UK-14,304-18 will lower intraocular pressure when microinjected into the medullary intermediate reticular zone region and that efaroxan, but not rauwolscine, will inhibit ocular hypotension induced by moxonidine and oxymetazoline [16].
• A double-blind comparison between oral pseudoephedrine and topical oxymetazoline in the prevention of barotrauma during air travel [17].
• Administration of phenylephrine and oxymetazoline for more than 2 weeks caused histologic changes including ciliary loss, epithelial ulceration, inflammatory cell infiltration and subepithelial edema, and the changes were more pronounced with increasing administration duration of the decongestants [18].

Biological context of oxymetazoline

• Subjective and objective increases in nasal airway resistance and mucus production induced by the allergen were significantly (p < 0.01) reduced after NPY pretreatment when compared with saline solution or oxymetazoline pretreatment [13].
• Vasoconstriction and local effects of L-NAME on NO synthesis are unlikely to explain this effect since oxymetazoline, a vasoconstrictor, decreased exhaled NO but had no effect on sleep onset latency [19].
• Further characterization of these binding sites indicated that the alpha 2-adrenergic receptor is of the alpha 2A subtype, since prazosin and ARC-239 bound with low affinities and oxymetazoline bound with high affinity [20].
• 4. It is concluded that noradrenaline and oxymetazoline stimulate gluconeogenesis in rat kidney via an alpha 1-rather than an alpha 2-type of adrenoceptor [21].
• After oxymetazoline instillation, resistance in the supine position decreased but remained higher in snorers than baseline value in the seated position [2].

Anatomical context of oxymetazoline

• 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 [22].
• In frontal cortex membranes, the competition curves with prazosin were steep, indicating a single class of binding sites, whereas the competition curves with oxymetazoline were shallow and fitted by computer best to a two-site model [23].
• The binding of [3H]rauwolscine to alpha 2A- (also referred to as alpha 2D-) and alpha 2C-adrenoceptors in homogenates of rat cerebral cortex was measured by exploiting the selectivity of oxymetazoline for alpha 2A-adrenoceptors [24].
• RESULTS: The alpha(2)-adrenoceptor agonists induced vasoconstriction in the porcine ciliary artery with the following potency order (EC(50)) expressed in nanomolar: brimonidine 2.11, oxymetazoline 5.26, and apraclonidine 13 [25].
• It was found that only the subjects who were treated with the combination of oxymetazoline nasal spray and benzalkonium chloride had increased nasal stuffiness, estimated by symptom scores and measurements of nasal mucosa swelling after 10 days of treatment [26].

Associations of oxymetazoline with other chemical compounds

• The secretin-induced stimulation of bile production was suppressed by phenylephrine, but not by oxymetazoline [27].
• Glucagon-stimulated glucose output was not suppressed even when cAMP in the effluent was significantly suppressed by oxymetazoline [27].
• 3. The selective alpha 1-adrenoceptor antagonist thymoxamine blocked the stimulatory effects on gluconeogenesis of noradrenaline and of oxymetazoline (a synthetic alpha-agonist) [21].
• 5. Compound D-600 opposed stimulation of gluconeogenesis by noradrenaline or oxymetazoline (a selective alpha-adrenoceptor agonist) in a manner suggesting that compound D-600 is an alpha-adrenoceptor blocker [28].
• The oxymetazoline, clonidine and antagonist inhibition curves were routinely monophasic and modeled best as a single class of binding sites [29].

Gene context of oxymetazoline

• The alpha-2A preferential agonist oxymetazoline induced in the mouse a hyperglycemic response similar to that of the nonselective alpha-2 adrenoceptor agonist UK 14.304 [30].
• Each of these RGS proteins altered the intrinsic activity of both UK14304 and oxymetazoline relative to adrenaline [31].
• Oxymetazoline, the relatively selective alpha 2A-adrenoceptor agonist (with more than 60-fold selectivity over the alpha 2B-adrenoceptor subtype), was administered into the lateral ventricle (i.c.v.) of rats and plasma growth hormone (GH) levels were measured [32].
• Intracerebroventricular (i.c.v) administration of human growth hormone (40 micrograms), neurotensin (2 micrograms), glucagon (25 micrograms) or intravenous (i.v.) injection of oxymetazoline (50 micrograms/kg b.w.), an alpha-adrenergic agonist, or endotoxin (150 micrograms/kg b.w.) suppressed subsequent GH surges [33].
• When oxymetazoline was injected i.c.v. to rats with somatostatin fibres to the median eminence transected by an anterolateral cut in the hypothalamus there was a significant rise in plasma GH, suggesting that oxymetazoline stimulated GHRH rather than inhibited somatostatin release [32].

Analytical, diagnostic and therapeutic context of oxymetazoline

• Oxymetazoline, an alpha 2 receptor agonist, induced a significant constriction only at 10(-3)M (5.1%) [34].
• On the other hand, topical administration of a decongestant drug, oxymetazoline (250 micrograms per guinea pig), had no effect on the response to antigen [35].
• Posterior rhinomanometry was performed in 70 snorers referred for polysomnography and in 11 nonsnoring volunteers, (1) in the seated posture; (2) and (3) after 10 minutes in the supine position, before and after inhalation of oxymetazoline; and (4) 10 minutes after return to the seated position [2].
• Abrupt withdrawal in a healthy man of oxymetazoline nasal spray precipitated a prolonged panic disorder that required hospitalization with extensive evaluations [6].
• On day 2 of HF diet, GIIS returned to normal after treatment with oxymetazoline, an alpha(2A)-adrenoreceptor agonist, thus suggesting the involvement of a low sympathetic tone in insulin hypersecretion in response to glucose in HF rats [36].

References