CYPROHEPTADINE HYDROCHLORIDE CAS 969-33-5
Introduction：Basic information about CYPROHEPTADINE HYDROCHLORIDE CAS 969-33-5, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
CYPROHEPTADINE HYDROCHLORIDE Basic information
| Product Name: | CYPROHEPTADINE HYDROCHLORIDE |
| Synonyms: | CYPROHEPTADINE HYDROCHLORIDE(GRP B SL NO.1124);Cycloheptadine Hydrochloride;1-methyl-4-(5-dibenzo(a,e)cycloheptatrienylidene)piperidinehydrochloride;4-(5-dibenzo(a,e)cycloheptatrienylidene)piperidinehydrochloride;4-(5h-dibenzo(a,d)cyclohepten-5-ylidene)-1-methyl-piperidinhydrochloride;cyproheptadienehydrochloride;nuran;4-(5H-DIBENZO[A,D]CYCLOHEPTEN-5-YLIDINE)-METHYLPIPERIDINE HYDROCHLORIDE |
| CAS: | 969-33-5 |
| MF: | C21H21N.ClH |
| MW: | 323.86 |
| EINECS: | 213-535-1 |
| Product Categories: | Serotonin receptor;Active Pharmaceutical Ingredients |
| Mol File: | 969-33-5.mol |
CYPROHEPTADINE HYDROCHLORIDE Chemical Properties
| Melting point | 254-256.5 °C(Solv: ethanol (64-17-5); ethyl ether (60-29-7)) |
| storage temp. | Inert atmosphere,Room Temperature |
| solubility | ethanol: soluble |
| form | solid |
| color | Crystals from EtOH/Et2O |
| Water Solubility | Soluble in water (15mM) |
| Stability: | Hygroscopic |
| Major Application | pharmaceutical (small molecule) |
| InChI | InChI=1S/C21H21N.ClH/c1-22-14-12-18(13-15-22)21-19-8-4-2-6-16(19)10-11-17-7-3-5-9-20(17)21;/h2-11H,12-15H2,1H3;1H |
| InChIKey | ZPMVNZLARAEGHB-UHFFFAOYSA-N |
| SMILES | CN1CC/C(/CC1)=C1/C2=CC=CC=C2C=CC2=CC=CC=C/12.Cl |
Safety Information
| Hazard Codes | Xn |
| Risk Statements | 22-36/37/38 |
| Safety Statements | 26-36 |
| RIDADR | UN 2811 6.1/PG 3 |
| WGK Germany | 3 |
| RTECS | TM7050000 |
| HazardClass | 6.1(b) |
| PackingGroup | III |
| Storage Class | 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Acute Tox. 4 Oral Eye Irrit. 2 Skin Irrit. 2 STOT SE 3 |
| Toxicity | LD50 orl-rat: 295 mg/kg DRUGAY 6,340,82 |
| Originator | Periactin,Merck Sharp andDohme,US,1961 |
| Uses | Antipruritic;5-HT antagonist |
| Uses | Cyproheptadine hydrochloride is an antihistamine in which antiserotoninactivity has been demonstrated both in vivo and in vitro. As yet, however,there is no evidence that this action contributes to clinical therapeuticeffects. Anticholinergic and sedative effects are observed. Cyproheptadine may be more effective than other H1 blockers in the management of coldurticaria. |
| Definition | ChEBI: The hydrochloride salt of cyproheptadine. Note that the drug named cyproheptadine hydrochloride generally refers to cyproheptadine hydrochloride sesquihydrate. |
| Manufacturing Process | (A) Preparation of 1-Methyl-4-Piperidyl-Magnesium Chloride: Magnesiumturnings (5.45 g, 0.22 g-atom) were placed in a 500 ml 3-necked flaskprovided with a condenser, Hershberg stirrer and dropping funnel andprotected with a drying tube. An atmosphere of dry nitrogen was maintainedin the apparatus throughout the reaction. The magnesium was covered with 20 ml of dry tetrahydrofuran. A crystal of iodine and 1.2 g of ethyl bromidewere added and after the reaction had subsided (formation of ethylmagnesiumbromide) a solution of 29.4 g (0.22 mol) of 4-chloro-1-methyl-piperidine indry tetrahydrofuran (total volume, 103 ml) was added dropwise at such a ratethat gentle reflux was maintained. The solution of 4-chloro-1-methylpiperidine in tetrahydrofuran was dried overcalcium hydride at ice-bath temperature prior to use. When the addition of thehalide was complete the reaction mixture was refluxed with stirring for onehour. In some subsequent experiments this period of refluxing was omittedwith no deleterious result. The solution of 4-chloro-1-methylpiperidine in tetrahydrofuran was dried overcalcium hydride at ice-bath temperature prior to use. When the addition of thehalide was complete the reaction mixture was refluxed with stirring for onehour. In some subsequent experiments this period of refluxing was omittedwith no deleterious result. The solvent was evaporated from the combined benzene extracts to give 33.4g of a clear light brown resin. Crystallization from an alcohol-water mixturegave 19.5 g of 1-methyl-4-(5-hydroxy-5-dibenzo[a,e]cycloheptatrienyl)-piperidine, MP 156° to 157°C. Two recrystallizations from alcohol-watermixtures followed by two recrystallizations from benzene-hexane mixturesgave analytically pure product, MP 166.7° to 167.7°C. (C) Preparation of 1-Methyl-4-(5-Dibenzo[a,e]Cycloheptatrienylidene)-Piperidine Hydrochloride: 1-Methyl-4-(5-hydroxy-5-dibenzo[a,e]cycloheptatrienyl)-piperidine (3.05 g, 0.01 mol) was dissolved in glacial aceticacid, 15 ml. The solution was saturated with dry hydrogen chloride withexternal cooling. A white solid separated. Acetic anhydride (3.07 g, 0.03 mol)was added and the mixture heated on the steam bath for one hour. The soliddissolved in the first 5 minutes of the heating period. The reaction mixture was poured into 25 ml of water and the mixture madestrongly basic with 10N sodium hydroxide solution. The mixture was extracted3 times with 50 ml portions of benzene, the combined extracts washed withwater and concentrated to a volume of approximately 50 ml. The solution wassaturated with dry hydrogen chloride and the white crystalline productcollected and dried. The yield of product, MP 251.6° to 252.6°C (dec.) was2.5 g. Recrystallization from a mixture of absolute alcohol and absolute ethergave a product, MP 252.6° to 253.6°C. A sample was analyzed after dryingfor 7 hours at 110°C over phosphorus pentoxide in vacuo. (D) Preparation of 1-Methyl-4-(5-Dibenzo[a,e]Cycloheptatrienylidene)-Piperidine: The hydrochloride salt, 4.3 g, was suspended in 100 ml of warmwater and the mixture made strongly alkaline by the addition of 15 ml of 5%sodium hydroxide. The mixture was extracted with four 50 ml portions ofbenzene and the extracts dried over sodium sulfate. Evaporation of thebenzene on the steam-bath at reduced pressure left 3.7 g (97%) of the base,MP 110.3° to 111.3°C. Recrystallization from a mixture of alcohol and watergave product, MP 112.3° to 113.3°C. |
| Brand name | Periactin (Merck). |
| Therapeutic Function | Antipruritic, Antihistaminic, Appetite stimulant |
| General Description | Cyproheptadinehydrochloride, 4-(5H-dibenzo-[a,d]-cyclohepten-5-ylidine)-1-methylpiperidine hydrochloride sesquihydrate(Periactin), is slightly soluble in water and sparingly solublein alcohol. Cyproheptadine possesses both antihistamine and antiserotoninactivity and is used as an antipruritic agent. It isindicated for the treatment of hypersensitivity reactions,perennial, and seasonal allergic rhinitis; vasomotor rhinitis;allergic conjunctivitis, uncomplicated allergic skin manifestationsof urticaria and angioedema; amelioration of allergicreactions to blood or plasma; and cold urticaria. It is alsoused off-label for nightmares associated with posttraumaticstress disorder (PTSD), prevention of migraine, suppressionof vascular headaches, and appetite stimulation. Sedation isthe most prominent side effect, and this is usually brief, disappearingafter 3 or 4 days of treatment. |
| Biological Activity | Non-selective 5HT 2 antagonist, migraine prophylactic. |
| Safety Profile | Poison by ingestion and intraperitoneal routes. Human systemic effects by ingestion: jaundice, liver function tests impaired, gastrointestinal effects. An experimental teratogen. Experimental reproductive effects. Human mutation data reported. Whenheated |
| Drug interactions | Potentially hazardous interactions with other drugs Analgesics: sedative properties increased with opioid analgesics. |
| Metabolism | Undergoes almost complete metabolism in the liver. The main metabolite found in humans is a quaternary ammonium glucuronide conjugate of cyproheptadine.40% is excreted in the urine mainly as metabolites and 2-20% via the faeces. |
| storage | Room temperature |
| references | [1] levine b, green-johnson d, hogan s, smialek je. a cyproheptadine fatality. j anal toxicol. 1998 jan-feb;22(1):72-4. [2] lin oa, karim za, vemana hp, espinosa ev, khasawneh ft. the antidepressant 5-ht2a receptor antagonists pizotifen and cyproheptadine inhibit serotonin-enhanced platelet function. plos one. 2014 jan 23;9(1):e87026. |
CYPROHEPTADINE HYDROCHLORIDE Preparation Products And Raw materials
| Raw materials | Acetic anhydride-->Hydrochloric acid-->Magnesium-->Sodium hydroxide-->4-Chloropiperidine hydrochloride-->Bromoethane-->5-(1-Methyl-4-Piperidyl)5H-Dibenzo |
