2-(Diphenylmethoxy)-N,N-dimethyl-ethanamin

Benadryl · Benzhydryl · Dimedrol · DIPHENHYDRAMINE BASE · Etanautine · Restamin · Benzhydril · Benzhydramine

Identifikatoren & physikalische Daten

CAS No.	147-24-0
Summenformel	C17H21NO
Durchschnittliche Molmasse	255,35 g/mol
Monoisotopische Masse	255,16231429 g/mol
SMILES	CN(C)CCOC(c1ccccc1)c1ccccc1
InChIKey	ZZVUWRFHKOJYTH-UHFFFAOYSA-N
PubChem CID	3100
ChEMBL	CHEMBL657
ChEBI	CHEBI:4636
EC No.	200-396-7
DTXSID	DTXSID4022949
Lokaler Name	2-(Diphenylmethoxy)-N,N-dimethyl-ethanamin

Chemische & physikalische Eigenschaften

XLogP	3,3
Polarare Oberfläche (TPSA)	12,5
H-Brücken-Donoren	0
H-Brücken-Akzeptoren	2
Frei drehbare Bindungen	6
Schwere Atome	19
Formalladung	0
Komplexität	211
Stoffklassen	Pharmaceutical
Arzneimittel	PharmaceuticalsPharmaceuticals -> Used in SwitzerlandPharmaceuticals -> Listed in ZINC15
LogP (Verteilungskoeffizient)	log Kow = 3.273.4
Color/Form	Oil
Löslichkeit	In water, 3.06X10+3 mg/L at 37 °CChloroform (Slightly), Methanol (Slightly)
Human Drugs	Breast FeedingLactationMilk, HumanAntihistamines
Animal Drugs	Pharmaceuticals -> Animal Drugs -> Approved in Taiwan
Siedepunkt	150-165 °C at 2.00E+00 mm HgBP: 165 °C at 3 mm HgBP: 150-165 °C at 2.0 mm Hgbp2.0 150-165°
Schmelzpunkt	161-162Crystals from absolute alcohol + ethermp: 166-170 °Cbitter tastepH of 1% aqueous solution about 5.51 g dissolves in: 1 mL water, 2 mL alcohol, 50 mL acetone, 2 mL chloroformvery slightly soluble in benzene, ether. Slowly darkens on exposure to light. Stable under ordinary conditions. /Diphenhydramine hydrochloride/168 °C167-172°C
Physical Description	Solid
Stability/Shelf Life	Slowly darkens on exposure to light. Stable under ordinary conditions /Diphenhydramine hydrochloride/
Dissociation Constants	9.18.98pKa = 8.98
Dichte	0.9889 (rough estimate)
Brechungsindex	1.5450 to 1.5490
Lagerbedingungen	Keep in dark place,Inert atmosphere,Room temperature
Aggregatzustand	Oil
pKa (Säurekonstante)	pKa 9.1 (Uncertain)
Farbe	Oil
Merck	14,3309
BCS Class	1
InChI	InChI=1S/C17H21NO/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h3-12,17H,13-14H2,1-2H3
InChIKey	ZZVUWRFHKOJYTH-UHFFFAOYSA-N
SMILES	C(N(C)C)COC(C1=CC=CC=C1)C1=CC=CC=C1
CAS Datenbank	58-73-1(CAS DataBase Reference)
NIST chemische Informationen	Ethylamine, 2-diphenylmethoxy-n,n-dimethyl-(58-73-1)
EPA chemische Informationen	Ethanamine, 2-(diphenylmethoxy)-N,N-dimethyl- (58-73-1)

Sicherheit & Vorschriften

GHS-Einstufung	WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P264+P265, P270, P280, P301+P317, P302+P352, P305+P351+P338, P321, P330, P332+P317, P337+P317, P362+P364, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 6 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Regulatorische Informationen	REACH registered substance: Diphenhydramine (EC: 200-396-7)Ethanamine, 2-(diphenylmethoxy)-N,N-dimethyl-: Does not have an individual approval but may be used under an appropriate group standard
FDA-Anforderungen	Antiemetic active ingredients. The active ingredient of the product consists of the following when used within the dosage limits established for each ingredient in section 336.50(d): Diphenhydramine hydrochloride. /Diphenhydramine hydrochloride/Nighttime sleep-aid active ingredients. The active ingredient of the product consists of the following when used within the dosage limits established for each ingredient in section 338.50(d): Diphenhydramine hydrochloride and diphenhydramine citrate. /Diphenhydramine hydrochloride and diphenhydramine citrate/Antihistamine active ingredients. The active ingredient of the product consists of the following when used within the dosage limits established for each ingredient: Diphenhydramine hydrochloride and diphenhydramine citrate. /Diphenhydramine hydrochloride and diphenhydramine citrate/Antitussive active ingredients. The active ingredients of the product consist the following when used within the dosage limits and in the dosage forms established for each ingredient in section 341.74(d): Diphenhydramine hydrochloride and diphenhydramine citrate. /Diphenhydramine hydrochloride and diphenhydramine citrate/For more FDA Requirements (Complete) data for DIPHENHYDRAMINE (7 total), please visit the HSDB record page.
Special Reports	DHHS/NTPToxicology & Carcinogenesis Studies of Diphenhydramine hydrochloride in F344/N Rats and B6C3F1 Mice (Feed Studies) Technical Report Series No. 355 (1989) NIH Publication No. 89-2810 /Diphenhydramine hydrochloride/
Toxic Combustion Products	Carbon oxides, nitrogen oxides (NOx), Hydrogen chloride gas. /Diphenhydramine hydrochloride/
Hazard Classes and Categories	Acute Tox. 4 (100%)
Brandbekämpfungsverfahren	Suitable extinguishing media Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Advise for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. /Diphenhydramine hydrochloride/
Lagerbedingungen	Keep container tightly closed in a dry and well-ventilated place. /Diphenhydramine hydrochloride/
Reinigungsverfahren	Personal precautions: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /Diphenhydramine hydrochloride/
Entsorgungsverfahren	SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product. /Diphenhydramine hydrochloride/
Preventive Measures	Hygiene measures: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday. /Diphenhydramine hydrochloride/Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Diphenhydramine hydrochloride/Diphenhydramine hydrochloride topical solution contains a flammable vehicle, and the solution should not be exposed to an open flame or ignited materials (e.g., a lighted cigarette).Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Diphenhydramine hydrochloride/
Personal Protective Equipment (PPE)	Hand protection: Handle with gloves. /Diphenhydramine hydrochloride/Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Diphenhydramine hydrochloride/Skin and body protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Diphenhydramine hydrochloride/Eye protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Diphenhydramine hydrochloride/
Treatment	There is no specific antidote for diphenhydramine toxicity, but the anticholinergic syndrome has been treated with physostigmine for severe delirium or tachycardia. Benzodiazepines may be administered to decrease the likelihood of psychosis, agitation, and seizures in patients who are prone to these symptoms.
Wechselwirkungen	Concurrent use /of ototoxic medications/ with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo. /Antihistamines/Concurrent use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong and intensify the anticholinergic and CNS depressant effects of antihistaminesconcurrent use is not recommended. /Antihistamines/Concurrent use /with alcohol or other CNS depression-producing medications/ may potentiate the CNS depressant effects of either these medications or antihistaminesalso, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications. /Antihistamines/Anticholinergic effects may be potentiated when /anticholinergics or other medications with anticholinergic activity/ are used concurrently with antihistaminespatients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy. /Antihistamines/For more Interactions (Complete) data for DIPHENHYDRAMINE (8 total), please visit the HSDB record page.
Gesundheitliche Auswirkungen	They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.
Hepatotoxicity	Despite widespread use over many decades, diphenhydramine has not been linked to liver test abnormalities or to clinically apparent liver injury. The reason for its safety may relate its short half-life and limited duration of use.
Ökotoxizitätswerte	EC50Species: Danio rerio (Zebra Danio) age 4 hr postfertilization embryo, wild-typeConditions: freshwater, static, 25 °C, pH 6.8-8, hardness 217-235 mg/L CaCO3, dissolved oxygen >80%Concentration: 0.35 mM for 20 hrEffect: abnormal development /formulation/Concentration: 0.14 mM for 44 hrConcentration: 0.15 mM for 68 hrConcentration: 0.02 mM for 140 hrFor more Ecotoxicity Values (Complete) data for DIPHENHYDRAMINE (7 total), please visit the HSDB record page.
Umweltverhalten	TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 380(SRC), determined from a log Kow of 3.27(2) and a regression-derived equation(3), indicates that diphenhydramine is expected to have moderate mobility in soil(SRC). The pKa of diphenhydramine is 8.98(4), indicating that this compound will exist almost entirley in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Diphenhydramine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.8X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation data in soil were not available(SRC, 2014).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 380(SRC), determined from a log Kow of 3.27(2) and a regression-derived equation(3), indicates that diphenhydramine is expected to adsorb to suspended solids and sediment(SRC). The pKa of diphenhydramine is 8.98(4) which indicates diphenhydramine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces and bioconcentration are not expected to be an important fate processes. Biodegradation data in water were not available(SRC, 2014).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diphenhydramine, which has an estimated vapor pressure of 5.8X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase diphenhydramine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 0.13 days(SRC), calculated from its rate constant of 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase diphenhydramine may be removed from the air by wet and dry deposition(SRC). Diphenhydramine does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
Unerwünschte Wirkungen	The following adverse effects have been observed in patients receiving diphenhydramine therapy.
Expositionspfade	Oraltopicalparenteral(intramuscular or intravenous injection). Quickly absorbed with maximum activity occurring in approximately one hour.
Toxizitätsübersicht	Signs and Symptoms of OverdoseDiphenhydramine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding.
Ökotoxizitätsauszüge	/AQUATIC SPECIES/ In recent years pharmaceuticals have been detected in aquatic systems receiving discharges of municipal and industrial effluents. Although diphenhydramine (DPH) has been reported in water, sediment, and fish tissue, an understanding of its impacts on aquatic organisms is lacking. Diphenhydramine has multiple modes of action (MOA) targeting the histamine H1, acetylcholine (ACh), and 5-HT reuptake transporter receptors, and as such is used in hundreds of pharmaceutical formulations. The primary objective of this study was to develop a baseline aquatic toxicological understanding of DPH using standard acute and subchronic methodologies with common aquatic plant, invertebrate, and fish models. A secondary objective was to test the utility of leveraging mammalian pharmacology information to predict aquatic toxicity thresholds. The plant model, Lemna gibba, was not adversely affected at exposures as high as 10 mg/L. In the fish model, Pimephales promelas, pH affected acute toxicity thresholds and feeding behavior was more sensitive (no-observed-effect concentration = 2.8 ug/L) than standardized survival or growth endpoints. This response threshold was slightly underpredicted using a novel plasma partitioning approach and a mammalian pharmacological potency model. Interestingly, results from both acute mortality and subchronic reproduction studies indicated that the model aquatic invertebrate, Daphnia magna, was more sensitive to DPH than the fish model. These responses suggest that DPH may exert toxicity in Daphnia through ACh and histamine MOAs. The D. magna reproduction no-observed-effect concentration of 0.8 ug/L is environmentally relevant and suggests that additional studies of more potent antihistamines and antihistamine mixtures are warranted./AQUATIC SPECIES/ Ceriodaphnia dubia were tested to evaluate the acute and chronic interactive effects of diphenhydramine and sertraline. Observed effects were compared with 2 reference toxicity models, the concentration addition model and the independent action model. Results indicate that the 2 drugs exhibit additive toxicity in C. dubia. In some cases, individually sublethal concentrations of the chemicals resulted in 100% mortality when combined, demonstrating the potentially severe impact of trace environmental contaminants.
Signs and Symptoms	Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death.
Ongoing Test Status	EPA has released the first beta version (version 0.5) of the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The beta version of the iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assaysSee the data in Chemical Explorer/[USEPAICSS Dashboard ApplicationAvailable from, as of March 28, 2014: http://actor.epa.gov/dashboard/]The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /Diphenhydramine hydrochloride/[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=147-24-0]
TSCA-Inventar-Status	TSCA listed
Zollcode	2922.19.7000
RTECS-Nr.	KR6825000
Toxizität	LD50 oral in rat: 390mg/kg
Gefahrstoffdaten	58-73-1(Hazardous Substances Data)

Anwendungen & Verwendung

Beschreibung

Diphenhydramine is one of the main representatives of antihistamine drugs that block H1 receptors. Besides antihistamine activity, diphenhydramine exhibits a local anesthetic effect, relaxes smooth muscle, and has sedative and soporific action.

Verwenden

Diphenhydramine also reduces muscle rigidity and general stiffness, and has a relatively minor effect on tremors.