Clemastine Fumarate
hs592 · tavist · Alagyl · agasten · lecasol · piloral · reconin · tavegil
Identifiers & Physical Properties
| CAS No. | 14976-57-9 |
|---|---|
| Molecular formula | C25H30ClNO5 |
| Average molar mass | 460 g/mol |
| Monoisotopic mass | 459.1812508 g/mol |
| SMILES | CN1CCC[C@@H]1CCO[C@](C)(c1ccccc1)c1ccc(Cl)cc1.O=C(O)/C=C/C(=O)O |
| InChIKey | PMGQWSIVQFOFOQ-YKVZVUFRSA-N |
| PubChem CID | 5281069 |
| ChEMBL | CHEMBL1200795 |
| ChEBI | CHEBI:3739 |
| EC No. | 239-055-2 |
| DTXSID | DTXSID6047785 |
Chemical & Physical Properties
| Topological polar surface area | 87.1 |
|---|---|
| Hydrogen bond donors | 2 |
| Hydrogen bond acceptors | 6 |
| Rotatable bonds | 8 |
| Heavy atoms | 32 |
| Formal charge | 0 |
| Complexity | 495 |
| Odor | Odorless |
| Color/Form | Colorless to faintly yellow crystalline powder |
| Solubility | Very slightly soluble in water and sparingly soluble in alcohol.DMSO: soluble5mg/mL (clear solutionwarmed) |
| Human Drugs | FDA approved drugs -> Active ingredient |
| Boiling point | 154 °C at 0.02 mm Hg154°C (rough estimate) |
| Melting point | 177-178 °C158-162°C |
| Other Experimental Properties | 154 °C at 0.02 mm Hg (free base) |
| alpha | D21 +16.9° (methanol) |
| Density | 1.0247 (rough estimate) |
| Refractive index | 1.5790 (estimate) |
| Storage conditions | 2-8°C |
| Physical state | powder |
| Color | white to beige |
| optical activity | [α]/D +15 to +25°, c = 1 in methanol |
| InChIKey | PMGQWSIVQFOFOQ-YKVZVUFRSA-N |
| SMILES | [C@@](C)(OCC[C@H]1CCCN1C)(C1C=CC=CC=1)C1=CC=C(Cl)C=C1.C(/C(=O)O)=C\C(=O)O |&1:0,5,r| |
| CAS DataBase Reference | 14976-57-9(CAS DataBase Reference) |
| FDA UNII | 19259EGQ3D |
| UNSPSC Code | 41116107 |
| NACRES | NA.77 |
| GHS pictogram | GHS07 |
| Signal word | Warning |
| GHS hazard statements | H302 |
| GHS precautionary statements | P280-P305+P351+P338 |
| Water hazard class (WGK) | 3 |
| RTECS number | UY0704600 |
| Customs code | 2933992600 |
| Storage class | 11 - Combustible Solids |
| Hazardous substances data | 14976-57-9(Hazardous Substances Data) |
| Toxicity | LD50 in mice, rats (mg/kg): 730, 3550 orally43, 82 i.v. (Weimann) |
Safety & Regulations
| GHS classification | This chemical does not meet GHS hazard criteria for 66.7% (12 of 18) of all reports.WarningH400 (22.2%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]P273, P391, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 18 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| FDA requirements | Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended21 U.S.C. 321-392).The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed drug products, incl clemastine fumarate, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /From the Prescription Drug Product List/ |
| Hazard Classes and Categories | Aquatic Acute 1 (22.2%) |
| Body burden | Following oral administration of 2.68 mg of clemastine fumarate daily for 3 days in one nursing woman, a milk clemastine concentration of about 5-10 ug/ml occurred 20 hours after the last dose of the drug. |
| Milk Concentrations | Following oral administration of 2.68 mg of clemastine fumarate daily for 3 days in one nursing woman, a milk clemastine concentration of about 5-10 ug/ml occurred 20 hours after the last dose of the drug. |
| Human Toxicity Excerpts | Usual therapeutic doses of clemastine interfere with color vision.Drowsiness, irritability, refusal to feed, and high-pitched cry occurred in one breast-fed infant (10 weeks of age) of a women who received 2.68 mg of clemastine fumarate daily for 3 days. |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)Clemastine fumaratevNo-DILI-concernNo matchDOI:10.1016/j.drudis.2016.02.015 |
Applications & Uses
Uses
anti-inflammatory
Uses
Clemastine fumarate is a selective histamine H1 receptor antagonist (Ki = 0.26 nM) that also displays high affinity for muscarinic receptors (Ki = 16 nM). It has also recently been identified as a positive allosteric modulator of P2X7 receptor signaling. Clemastine fumarate has long been used to inhibit histamine-induced bronchoconstriction in asthma and airway hyperresponsive studies.
Uses
H1 Histamine receptor antagonist. Antihistaminic.
General Description
Dextrorotatory clemastine, R,R-2[2[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1- methylpyrrolidine hydrogen furnarate (1:1) (Tavist), has two chiral centers, each of which has the (R) absolute configuration. A comparison of the activities of the enantiomers indicates that the asymmetric center close to the terminal side chain nitrogen is of lesser importance to antihistaminic activity. This member of the ethanolamine series is characterized by a long duration of action, with an activity that reaches a maximum in 5 to 7 hours and persists for 10 to 12 hours. It is well absorbed when administered orally, and it is excreted primarily in the urine. The side effects are those usually encountered with this series of antihistamines. Clemastine is closely related to chlorphenoxamine, which is used for its central cholinergic-blocking activity. Therefore, it is not surprising that clemastine has significant antimuscarinic activity.