3-((4,5-Dihydro-1H-imidazol-2-yl)-methyl)-6-(11-dimethylethyl)-2,4-dimethylphenol

afrin · Oxymethazoline · h990 · Hazol · H-990 · nasivin · Nafrine · Iliadin

Identifikatoren & physikalische Daten

CAS No.	1491-59-4
Summenformel	C16H24N2O
Durchschnittliche Molmasse	260,37 g/mol
Monoisotopische Masse	260,18886339 g/mol
SMILES	Cc1cc(C(C)(C)C)c(O)c(C)c1CC1=NCCN1
InChIKey	WYWIFABBXFUGLM-UHFFFAOYSA-N
PubChem CID	4636
ChEMBL	CHEMBL762
ChEBI	CHEBI:7862
EC No.	216-079-1
DTXSID	DTXSID3040691
Lokaler Name	3-((4,5-Dihydro-1H-imidazol-2-yl)-methyl)-6-(11-dimethylethyl)-2,4-dimethylphenol

Chemische & physikalische Eigenschaften

XLogP	2,9
Polarare Oberfläche (TPSA)	44,6
H-Brücken-Donoren	2
H-Brücken-Akzeptoren	2
Frei drehbare Bindungen	3
Schwere Atome	19
Formalladung	0
Komplexität	345
Arzneimittel	Pharmaceuticals -> Listed in ZINC15
LogP (Verteilungskoeffizient)	3.4
Color/Form	Crystals from benzene
Löslichkeit	ODORLESSWHITE TO NEARLY WHITE, FINE, CRYSTALLINE POWDERSOL IN ALCMol wt 296.84. Crystals, dec 300-303 °C. Freely sol in water, alcohol. Practically insol in ether, chloroform, benzene /Hydrochloride/Insoluble in diethyl ether, chloroform, and benzene5.15e-02 g/L
Human Drugs	Breast FeedingLactationMilk, HumanAdrenergic alpha-AgonistsSympathomimeticsNasal DecongestantsFDA approved drugs -> Active ingredientPharmaceuticals
Decomposition	When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
Schmelzpunkt	181-183 °C182 °C
Physical Description	Solid
Stability/Shelf Life	STABLE IN LIGHT & HEAT, & IS NONHYGROSCOPIC /HYDROCHLORIDE/
Collision Cross Section	163.86 Å² [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]
Siedepunkt	403.63°C (rough estimate)
Dichte	0.9822 (rough estimate)
Brechungsindex	1.5800 (estimate)
pKa (Säurekonstante)	11.93±0.28(Predicted)
Farbe	Crystals from C6H6
InChI	InChI=1S/C16H24N2O/c1-10-8-13(16(3,4)5)15(19)11(2)12(10)9-14-17-6-7-18-14/h8,19H,6-7,9H2,1-5H3,(H,17,18)
InChIKey	WYWIFABBXFUGLM-UHFFFAOYSA-N
SMILES	C1(O)=C(C(C)(C)C)C=C(C)C(CC2NCCN=2)=C1C
CAS Datenbank	1491-59-4(CAS DataBase Reference)
NIST chemische Informationen	Oxymetazoline(1491-59-4)

Sicherheit & Vorschriften

GHS-Einstufung	DangerH300+H330 (96.6%): Fatal if swallowed or if inhaled [Danger Acute toxicity, oralacute toxicity, inhalation]P260, P264, P264+P265, P270, P271, P273, P280, P284, P301+P316, P304+P340, P305+P354+P338, P316, P317, P320, P321, P330, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 29 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Regulatorische Informationen	Chemical: Phenol, 3-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)-2,4-dimethyl-Status: Active Update: 06-02-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/22185
Weitere Sicherheitsinformationen	IMAP assessments - Phenol, 3-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)-2,4-dimethyl-: Environment tier I assessment
FDA-Anforderungen	Nasal decongestant active ingredients. The active ingredient of the product consists of any of the following when used within the dosage limits and in the dosage forms established for each ingredient: ... Topical nasal decongestants: Oxymetazoline hydrochloride. /Oxymetazoline hydrochloride/The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed over-the-counter drug products, incl oxymetazoline, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Special Reports	Gilstrap LC, Little BBDrugs & Pregnancy 269-75 (1992). Antihistamines, decongestants, and expectorants during pregnancy.Smith MB, Feldman WJAMA 269: 2256-63 (1993). Over the counter cold medications: critical review of clinical trials between 1950 and 1991.
Hazard Classes and Categories	Acute Tox. 1 (100%)
Lagerbedingungen	Oxymetazoline hydrochloride nasal solutions should be stored in tight containers at a temperature less than 40 °C, preferably at 2-30 °Cfreezing should be avoided. Oxymetazoline hydrochloride ophthalmic solutions should be stored at 15-30 °C. Oxymetazoline is probably degraded in the presence of aluminum and, therefore, should not be stored in aluminum containers.
Entsorgungsverfahren	SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
Wechselwirkungen	If significant systemic absorption of nasal /or ophthalmic/ oxymetazoline occurs, concurrent use of maprotiline or tricyclic antidepressants may potentiate the pressor effect of oxymetazoline.A case is described in which a 34 yr old man presented with severe hypertension, cardiomegaly, and congestive heart failure, presumably due to oxymetazoline hydrochloride, phenylephrine hydrochloride, and ephedrine hydrochloride, consumed in massive doses by an overuse of nasal decongestants and cough syrup. Coadamin chlorpromazine hydrochloride and trimeprazine tartrate may have contributed to the effects through anticholinergic and antihistamine properties. The patient was treated with furosemide and nifedipine. Signs and symptoms of heart failure quickly resolved and blood pressure dropped to 140/100 mm Hg. /Oxymetazoline hydrochloride/Self-treatment of anaphylaxis due to a single 75 mg dose of ketoprofen is reported in a 39 yr old female patient who used 12 inhalations of an oxymetazoline nasal solution in each nostril to relieve the respiratory symptoms of the allergic reaction. Within min of using the nasal solution, the respiratory symptoms began to subside, and the patient slept through the night and consulted her doctor the next day.Reported is a case of chronic hallucination in a 61-yr-old man associated with long term use of phenylephrine hydrochloride (Neo-Synephrine), and, more recently, oxymetazoline hydrochloride (Afrin) nasal preparations. Trifluoperazine hydrochloride (10 mg/day) was begun, nasal preparations were discontinued, and a combination of pseudoephedrine hydrochloride and tripolidine hydrochloride (Actifed) was given 2 times/day. The nasal obstruction gradually decreased and the symptoms of psychosis and anxiety were alleviated.
Human Toxicity Excerpts	/SIGNS AND SYMPTOMS/ Excessive dosage and/or prolonged or too frequent intranasal use of oxymetazoline may irritate nasal mucosa and, especially in children, cause adverse systemic effects. Excessive dosage or inadvertent ingestion in children may cause profound CNS depression, possibly necessitating intensive supportive care. CNS depression, shock-like hypotension, and coma have occurred following overdosage of naphazoline and tetrahydrozolinethe possibility that this may occur with oxymetazoline should be considered./CASE REPORTS/ In this incident, oxymetazoline nasal spray 0.025% was administered to a 2-year-old patient during general anesthesia for nasal endoscopy. Severe hypertension with reflex bradycardia progressed to sinus arrest and was successfully treated with atropine and cardiopulmonary resuscitation./CASE REPORTS/ A patient prescribed oxymetazoline hydrochloride nasal drops presented with recurrent ventricular tachycardia of fascicular origin. Cardiac ultrasound showed a calcified lesion, presumably a fibroma arising from the interventricular septum. Fascicular tachycardia related to the lesion and provoked by the use of a sympathomimetic agent is postulated./CASE REPORTS/ Oxymetazoline is a sympathomimetic amine found in over-the-counter nasal decongestants. A case of chronic use of nasal oxymetazoline associated with thunderclap headache due to reversible segmental intracranial vasoconstriction /is reported/.For more Human Toxicity Excerpts (Complete) data for OXYMETAZOLINE (11 total), please visit the HSDB record page.
Non-Human Toxicity Excerpts	/LABORATORY ANIMALS: Acute Exposure/ ... Oxymetazoline injected icvt /intracerebroventricular injection/ into the lateral ventricle of NZW rabbits induced bilateral ocular hypotension (> 7.0 mmHg) that peaked at 2 hr. Unilateral topical application of oxymetazoline induced maximal, bilateral hypotension (> 12 mm/Hg), at 3 hr, in both the contralateral and ipsilateral eyes, that persisted more than 12 hr. .../LABORATORY ANIMALS: Neurotoxicity/ To determine if intrathecal oxymetazoline induces histological evidence of spinal neurotoxicity, male, Sprague-Dawley rats (300-450 gimplanted with an intrathecal catheter) were treated with intrathecal saline or 100 nmol oxymetazoline twice daily for 3 days, or 200 or 300 nmol oxymetazoline once daily for 3 days. Spantide (D-Arg1, D-Try7,9, Leu11-substance P0.067 nmol = 0.1 ug, 0.167 nmol = 0.25 ug or 0.334 nmol = 0.5 ug) or capsaicin (0.164 mumol = 50 ug), given as a single intrathecal injection, were used as positive controls. Animals were killed 12 hr after the last injection of saline or oxymetazoline, and 72 hr after spantide or capsaicin. Spinal cord sections (L1 and adjacent segments) were examined by light microscopy for changes in gross morphology, substance P-like immunoreactivity (SP-IR) and calcitonin gene related peptide-like immunoreactivity (CGRP-IR). All doses of intrathecal oxymetazoline produced antinociception (tail-flick ED50 = 53.7 nmol, paw pressure withdrawal ED50 = 93.3 nmol). Rectal temperature decreased by 1.5-2.4 degrees C up to 12 hr after 100 nmol of intrathecal oxymetazoline. There were no signs of inflammation or necrosis, and no detectable loss or damage to either spinal afferents or motor neurons as judged by SP-IR and CGRP-IR structures in spinal cords of oxymetazoline-treated animals (all doses) as compared to intrathecal saline controls. Spantide (0.1 ug) had no antinociceptive or neurotoxic effect0.25 ug induced irreversible loss of the TF reflex and transient hind limb paralysis0.5 microgram induced irreversible loss of TF and PP responses, permanent hind limb paralysis, bladder and bowel dysfunction. The spinal cords from these animals showed signs of extensive necrosis, cavitation, and hemorrhage in the ventral horn accompanied by a loss of CGRP-IR motor neurons. Capsaicin-treated rats exhibited a permanent loss of the TF but not the PP response and a marked reduction of SP-IR spinal afferents in the dorsal horn. It is concluded that i.t. oxymetazoline produces antinociception in the rat with no detectable spinal neurotoxicity as assessed by parameters which are sensitive to the neurotoxins, spantide and capsaicin./OTHER TOXICITY INFORMATION/ In dogs, signs of intoxication may include vomiting, bradycardia, cardiac arrhythmias, poor capillary refill time, hypotension or hypertension, panting, increased upper respiratory sounds, depression, weakness, nervousness, hyperactivity, or shaking. These signs appear within 30 min to 4 hr postexposure. In general, imidazoline decongestant exposure may affect the GI, cardiopulmonary, and nervous systems. /Imidazoline decongestions/
Antidote and Emergency Treatment	/VET:/ Decontamination may not be practical due to the rapid absorption and onset of clinical signs. Heart rate and rhythm and blood pressure should be assessed, and an ECG obtained if needed. IV fluids should be given, along with atropine at 0.02 mg/kg, IV, if bradycardia is present. Diazepam (0.25-0.5 mg/kg, IV) can be given if CNS signs (eg, apprehension, shaking) are present. Serum electrolytes (ie, potassium, sodium, chloride) should be assessed and corrected as needed. Yohimbine, which is a specific a2-adrenergic antagonist, can also be used at 0.1 mg/kg, IV, and repeated in 2-3 hr if needed. /Imidazoline decongestants/
Effects During Pregnancy and Lactation	◉ Summary of Use during Lactation◈ What is oxymetazoline?
Non-Human Toxicity Values	LD50 Rat oral 800 ug/kgLD50 Rat sc 1100 ug/kg
UN-Transportnummer	3249
Toxizität	LD50 orl-rat: 800 mg/kg TXAPA9 18,185,71
Gefahrenklasse	6.1(a)
Verpackungsgruppe	II
Gefahrstoffdaten	1491-59-4(Hazardous Substances Data)

Anwendungen & Verwendung

Verwenden

Oxymetazoline is used for the same indications as naphazoline, primarily for rhinitis.