HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
(+)-Pseudo-Ephedrin
psi-Ephedrin · D-PSEUDOEPHEDRINE · (1S,2S)-2-(METHYLAMINO)-1-PHENYLPROPAN-1-OL · (+)-Pseudoephedrine · (1S,2S)-(+)-PSEUDOEPHEDRINE · d-Pseudoephedrine base · Besan · Isoephedrine
Identifikatoren & physikalische Daten
| CAS No. | 4125-58-0 |
|---|---|
| Summenformel | C10H15NO |
| Durchschnittliche Molmasse | 165,23 g/mol |
| Monoisotopische Masse | 165,1153641 g/mol |
| SMILES | CN[C@@H](C)[C@@H](O)c1ccccc1 |
| InChIKey | KWGRBVOPPLSCSI-WCBMZHEXSA-N |
| PubChem CID | 7028 |
| ChEMBL | CHEMBL1590 |
| ChEBI | CHEBI:51209 |
| EC No. | 202-018-6 |
| DTXSID | DTXSID0023537 |
| Lokaler Name | (+)-Pseudo-Ephedrin |
Chemische & physikalische Eigenschaften
| XLogP | 0,9 |
|---|---|
| Polarare Oberfläche (TPSA) | 32,3 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 2 |
| Frei drehbare Bindungen | 3 |
| Schwere Atome | 12 |
| Formalladung | 0 |
| Komplexität | 121 |
| Stoffklassen | Pharmaceutical |
| Arzneimittel | Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive CompoundsPharmaceuticals -> Used in SwitzerlandPharmaceuticals -> Listed in ZINC15 |
| pH | AQ SOLN (1 IN 200) 10.8 |
| SpringerMaterials Properties | Crystal structure |
| LogP (Verteilungskoeffizient) | log Kow = 0.891.14 |
| Color/Form | Crystals from ether |
| Löslichkeit | Sparingly sol in waterfreely sol in alc or etherVERY SOL IN BENZENEDMF: 30 mg/mlDMSO: 30 mg/mlEthanol: 30 mg/mlPBS (pH 7.2): 5 mg/ml<0.5g/L(er) |
| Human Drugs | Breast FeedingLactationMilk, HumanAdrenergic AgentsAdrenergic Alpha-AgonistsCentral Nervous System StimulantsSympathomimeticsVasoconstrictor AgentsPharmaceuticals |
| Schmelzpunkt | 118-118.7 °CFINE, WHITE TO OFF-WHITE CRYSTALS OR POWDERFAINT CHARACTERISTIC ODORMP: 182-185 °CSOLN ARE NEUTRAL TO LITMUS /HCL/119 °C118-120 °C |
| Optical Rotation | Specific optical rotation: +51.2 deg at 20 °C/D (in ethanol) |
| Physical Description | Solid |
| Dissociation Constants | 10.3 (at 0 °C)pKa = 10.25 (conjugate acid) |
| Siedepunkt | 293.09°C (rough estimate) |
| Dichte | 1.0203 (rough estimate) |
| Dampfdruck | 0.016-0.032Pa at 20-25℃ |
| Brechungsindex | 1.5200 (estimate) |
| Flammpunkt | 9℃ |
| Lagerbedingungen | -20°C |
| Aggregatzustand | Crystalline |
| pKa (Säurekonstante) | pKa 9.73(H2O,t=25±0.5,I=0.01)(Approximate) |
| Merck | 13,8007 |
| BRN | 2414132 |
| Stabilität | Stable. Combustible. Incompatible with strong oxidizing agents. May discolour upon exposure to light. |
| InChI | 1S/C10H15NO/c1-8(11-2)10(12)9-6-4-3-5-7-9/h3-8,10-12H,1-2H3/t8-,10+/m0/s1 |
| InChIKey | KWGRBVOPPLSCSI-WCBMZHEXSA-N |
| SMILES | CN[C@@H](C)[C@@H](O)c1ccccc1 |
| LogP (Verteilungskoeffizient) | 0.89 at 25℃ |
| CAS Datenbank | 90-82-4(CAS DataBase Reference) |
| NIST chemische Informationen | Pseudoephedrine, (+)-(90-82-4) |
| EPA chemische Informationen | Benzenemethanol, .alpha.-[(1S)-1-(methylamino)ethyl]-, (.alpha.S)- (90-82-4) |
Sicherheit & Vorschriften
| GHS-Einstufung | WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P264+P265, P270, P271, P272, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 156 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | List I Chemical: A chemical specified by regulation that, in addition to legitimate uses, is used in manufacturing a controlled substance in violation of the Act and is important to the manufacture of a controlled substance. (21 eCFR 1310.02)Status: Active Update: 09-07-2013 https://echa.europa.eu/registration-dossier/-/registered-dossier/10032 |
| Weitere Sicherheitsinformationen | IMAP assessments - Benzenemethanol, .alpha.-[1-(methylamino)ethyl]-, [S-(R*,R*)]-: Human health tier I assessment |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription and over-the-counter drug products, incl pseudoephedrine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Pseudoephedrine Sulfate/The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription and over-the-counter drug products, incl pseudoephedrine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Pseudoephedrine Hydrochloride/The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products. Pseudoephedrine polistirex is included on this list.. /Pseudoephedrine Polistirex /Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: pseudoephedrine hydrochloride and pseudoephedrine sulfate are included in bronchodilator drug products. /Pseudoephedrine Hydrochloride, Pseudoephedrine Sulfate/The Combat Methamphetamine Epidemic Act of 2005 has been incorporated into the Patriot Act signed by President Bush on March 9, 2006. The act bans over-the-counter sales of cold medicines that contain the ingredient pseudoephedrine, which is commonly used to make methamphetamine. The sale of cold medicine containing pseudoephedrine is limited to behind the counter. The amount of pseudoephedrine that an individual can purchase each month is limited and individuals are required to present photo identification to purchase products containing pseudoephedrine. In addition, stores are required to keep personal information about purchasers for at least two years. |
| Special Reports | Bradley JGPostgrad Med 89 (6): 195-7 (1991). Nonprescription drugs and hypertension. Which ones affect blood pressure?Anastasio GD, Harston PRJ Am Board Family Pract 5 (5): 527-8 (1992). Fetal tachycardia associated with maternal use of pseudoephedrine, an over the counter oral decongestant.Hanzlick RToxicology 107 (2): 153-8 (1996). National Association of Medical Examiner's Pediatric Toxicology (PedTox) Registry.Gilstrap LC, Little BBDrugs & Pregnancy 269-75 (1992). Antihistamines, decongestants, and expectorants during pregnancy. |
| Hazard Classes and Categories | Acute Tox. 4 (100%) |
| Lagerbedingungen | Pseudoephedrine hydrochloride preparation should generally be stored at 15-30 °Cfreezing of the oral solution should be avoided. Pseudoephedrine hydrochloride tablets and extended release capsules should be stored in tight containers and oral solution in tight, light-resistant containers. Pseudoephedrine sulfate extended release tablets should be protected from light and stored in well-closed containers at 2-30 °C. |
| 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 | Administration of pseudoephedrine prior to or shortly after anesthesia with chloroform, cyclopropane, halothane, or trichloroethylene may increase the risk of severe ventricular arrhythmias, especially in patients with pre-existing heart disease, because these anesthetics greatly sensitize the myocardium to the effects of sympathomimetics.Enflurane, isoflurane, or methoxyflurane may also cause some sensitization of the myocardium to the effects of sympathomimeticscaution is recommended in patients taking pseudoephedrine.Antihypertensive effects may be reduced when these medications /antihypertensives or diuretics used as antihypertensives/ are used concurrently with pseudoephedrinethe patient should be carefully monitored to confirm that the desired effects is being obtained.Concurrent use /of beta-adrenergic blocking agents/ with pseudoephedrine may inhibit the therapeutic effect of these medicationsbeta-blockade may result in unopposed alpha-adrenergic activity of pseudoephedrine with a risk of hypertension and excessive bradycardia and possible heart block.For more Interactions (Complete) data for PSEUDOEPHEDRINE (17 total), please visit the HSDB record page. |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 73(SRC), determined from a log Kow of 0.89(2) and a regression-derived equation(3), indicates that pseudoephedrine is expected to have high mobility in soil(SRC). However, the pKa of pseudoephedrine is 10.25(4), indicating that this compound will primarily exist in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Pseudoephedrine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.3X10-4 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2007).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 73(SRC), determined from a log Kow of 0.89(2) and a regression-derived equation(3), indicates that pseudoephedrine is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 10.25(4) indicates pseudoephedrine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2007).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), pseudoephedrine, which has an estimated vapor pressure of 8.3X10-4 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 pseudoephedrine 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 4 hours(SRC), calculated from its rate constant of 9.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Pseudoephedrine does not contains chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(4). |
| Expositionspfade | Pseudoephedrine is readily and almost completely absorbed from the GI tract and there is no evidence of first-pass metabolism. |
| Milk Concentrations | EXPERIMENTAL: Drug Concentrated in Human Milk. /from Table 6/EXPERIMENTAL: Plasma and milk concentrations of pseudoephedrine and triprolidine were determined (by radioimmunoassay) in three lactating mothers over 12-48 hr after ingestion of a combination medication containing 60 mg of pseudoephedrine hydrochloride and 2.5 mg of triprolidine hydrochloride monohydrate. Pseudoephedrine concentrations in milk were consistently higher than those in plasma. The total amount of drug in milk, as judged by areas under the respective curves (AUC), was two to three times greater than in plasma. Triprolidine concentrations in milk and plasma were more variable between subjects than those of pseudoephedrine. AUC values for milk and plasma were similar for one subject, while the plasma value exceeded that for milk in another woman. The fraction of the dose excreted in milk was estimated to be 0.4-0.7% for pseudoephedrine and 0.06-0.2% for triprolidine.EXPERIMENTAL: Pseudoephedrine distributes into breast milkabout 0.5% of an oral dose is distributed into breast milk over 24 hours. |
| Toxizitätsübersicht | Pseudoephedrine acts directly on both alpha- and, to a lesser degree, beta-adrenergic receptors. Through direct action on alpha-adrenergic receptors in the mucosa of the respiratory tract, pseudoephedrine produces vasoconstriction. Pseudoephedrine relaxes bronchial smooth muscle by stimulating beta2-adrenergic receptors. Like ephedrine, pseudoephedrine releasing norepinephrine from its storage sites, an indirect effect. This is its main and direct mechanism of action. The displaced noradrenaline is released into the neuronal synapse where it is free to activate the postsynaptic adrenergic receptors. |
| Signs and Symptoms | Common adverse reactions include nervousness, restlessness, and insomnia. Rare adverse reactions include difficult/painful urination, dizziness/lightheadedness, heart palpitations, headache, increased sweating, nausea/vomiting, trembling, troubled breathing, unusual paleness, and weakness. |
| Soil Adsorption/Mobility | The Koc of pseudoephedrine is estimated as 73(SRC), using a log Kow of 0.89(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that pseudoephedrine is expected to have high mobility in soil. However, the pKa of pseudoephedrine is 10.25(4), indicating that this compound will primarily exist 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). |
| Natural Pollution Sources | Sympathomimetic amine found in plants of the genus Ephedra (Ephedraceae) known in traditional medicine as Ma Huang |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ Pseudoephedrine is contained in decongestants such as the Sudafed line of products. ... Two analyses of health maintenance organization pharmacy data identified 9 malformed infants among 902 first-trimester pseudoephedrine exposures, suggesting no association with birth defects overallhowever, studies of such data sets often lack sufficient power to identify risks for specific birth defects. The related compounds, epinephrine, ephedrine, and phenylephrine, have been associated with hemorrhages and cardiovascular and limb malformations in animal models. Risk of ventricular septal defects was associated with decongestant use in pregnant women in 1 recent study. The vasoconstrictive effects of these drugs raise the hypothesis that their use in early pregnancy might increase the risk of vascular disruption defects. Case-control studies, which often do have power to identify risks related to specific birth defects, have explored this hypothesis. Decongestant use in the first trimester has been associated with small increases in risks of 3 defects thought to arise, at least in some instances, from vascular disruption-gastroschisis, small intestinal atresia, and hemifacial microsomia. These findings are somewhat consistent in terms of magnitude of effect and suggest that risks are even greater among women also exposed to the vasoconstrictive effects of cigarette smoking. There are, however, limitations to these studies, including the possibilities of inaccurate recall of exposures and confounding by indication. In addition, the majority of decongestant use is in oral form and the question of whether intranasal formulations carry risk has not been adequately addressed./SIGNS AND SYMPTOMS/ Symptoms of overdose: Convulsionsfast breathinghallucinationsincrease in blood pressureirregular heartbeat, continuingshortness of breath or troubled breathing, severe or continuingslow or fast heartbeat, severe or continuingunusual nervousness, restlessness, or excitement./CASE REPORTS/ ... /The authors/ report a case of intracerebral hemorrhage occurring in a middle-aged man who suffered from chronic sinusitis and had been ingesting pseudoephedrine daily for one year. This patient was previously well with no known cardiovascular risk factors. Clinical examination revealed no evidence of vasculitis nor coagulopathy and initial neuroimaging (i.e., computed tomography, angiography, magnetic resonance imaging) demonstrated no features consistent with aneurysm, arteriovenous malformation, cavernoma, nor cerebral metastases. A follow-up cerebral angiogram demonstrated a small arteriovenous malformation arising off a branch of the pericallosal artery and a small arteriovenous fistula arising off the costal marginal branch. The arteriovenous malformation was embolized without incident, however, the arteriovenous fistula was not accessible. ... There is a paucity of literature etiologically inculpating other ephedra alkaloids in the causation of intracerebral hemorrhage. This is a case of pseudoephedrine-induced intracerebral hemorrhage in a patient with an underlying vascular malformation./CASE REPORTS/ We present a case of a 7 year old girl who developed an episode of myoclonic movements and tremors after being medicated with a not well quantified amount of a pseudoephedrine/antihistamine combination. We want to highlight the potential toxicity of pseudoephedrine, usually administered as part of cold-syrup preparations which are used for symptomatic treatment of upper respiratory tract cough and congestion associated with the common cold and allergic rhinitis. Although these products are generally considered to be safe either by physicians and parents, we can't underestimate the potential adverse events and toxic effects that can occur when administering these medications.For more Human Toxicity Excerpts (Complete) data for PSEUDOEPHEDRINE (20 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Pseudoephedrine's production and use as a decongestant(1) may result in its release to the environment through various waste streams(SRC). |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)pseudoephedrineDILI NegativeOralDOI:10.1016/j.drudis.2019.09.022 |
| Wassergefährdungsklasse (WGK) | 3 |
| TSCA-Inventar-Status | TSCA listed |
| UN-Transportnummer | 1544 |
| RTECS-Nr. | UL5800000 |
| R-Sätze (R) | 20/21/22-36/37/38-39/23/24/25-23/24/25-11 |
| Toxizität | LD50 oral in rat: 660mg/kg |
| Gefahrensymbole | Xn,T,F |
| Sicherheitshinweise (S) | 26-37/39-45-36/37-16-7 |
| Gefahrenklasse | 6.1(b)Acute Tox. 4 OralEye Irrit. 2Skin Irrit. 2STOT SE 3 |
| Verpackungsgruppe | III |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 90-82-4(Hazardous Substances Data) |
Anwendungen & Verwendung
Beschreibung
Pseudoephedrine is a stereoisomer of ephedrine, in the drug class of sympathomimetics. It occurs naturally in plants of the genus Ephedra. Pseudoephedrine is a mixed-acting decongestant, which activates α- and β-adrenergic receptors directly by binding to the receptor itself, and indirectly by causing norepinephrine release in synaptic nerve terminals. Pseudoephedrine is also used illicitly in the production of methamphetamine. In the United States, two recent acts of legislation – the Combat Methamphetamine Epidemic Act of 2005 and the Methamphetamine Production Prevention Act of 2008– have created stringent regulation on the sale of pseudoephedrine without a prescription. Pseudoephedrine-containing products were moved behind the counter, only to be sold by the pharmacist using their professional judgment and discretion. Limitations on the quantity of pseudoephedrine that could be purchased at one time and over a period of timewere enacted, and strict record keeping was required.
Verwenden
Pseudoephedrine is an orally active sympathomimetic amine that is used as a nasal decongestant. It exerts its decongestant action by acting directly on a-adrenergic receptors in the respiratory tract mucosa producing vasoconstriction resulting in shrinkage of swollen nasal mucous membranes, reduction of tissue hyperemia, edema, and nasal congestion, and an increase in nasal airway patency. Drainage of sinus secretions is increased and obstructed eustachian ostia may be opened. Relaxation of bronchial smooth muscle by stimulation of b-adrenergic receptors may also occur.