| Identification | Back Directory | [Name]
CYPROHEPTADINE HYDROCHLORIDE | [CAS]
969-33-5 | [Synonyms]
nuran
peritol
ANAREXOL
periactinsyrup
CYPROHEPTADINE HCL
CYPROHEPTADINE HCL BP
periactinhydrochloride
periactinolhydrochloride
cyproheptadienehydrochloride
Cyproheptadine hydrochloride
CyproheptadineHclCyproheptadineHclBp
CYPROHEPTADINEHYDROCHLORIDE(ANHYDROUS)
Cyproheptadine hydrochloride (Periactin)
CYPROHEPTADINE HYDROCHLORIDE(GRP B SL NO.1124)
4-(5-dibenzo(a,e)cycloheptatrienylidene)piperidinehydrochloride
4-(5H-DIBENZO[A,D]CYCLOHEPTEN-5-YLIDINE)-METHYLPIPERIDINE HYDROCHLORIDE
4-(5h-dibenzo(a,d)cyclohepten-5-ylidene)-1-methyl-piperidinhydrochloride
1-methyl-4-(5-dibenzo(a,e)cycloheptatrienylidene)piperidinehydrochloride | [EINECS(EC#)]
213-535-1 | [Molecular Formula]
C21H22ClN | [MDL Number]
MFCD00012538 | [MOL File]
969-33-5.mol | [Molecular Weight]
323.86 |
| Chemical Properties | Back Directory | [Melting point ]
254-256.5 °C(Solv: ethanol (64-17-5); ethyl ether (60-29-7)) | [storage temp. ]
Store at RT | [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 |
| Hazard Information | Back Directory | [Uses]
Antipruritic;5-HT antagonist | [Definition]
ChEBI: The hydrochloride salt of cyproheptadine. Note that the drug named cyproheptadine hydrochloride generally refers to cyproheptadine hydrochloride sesquihydrate. | [Biological Activity]
Non-selective 5HT 2 antagonist, migraine prophylactic. | [Originator]
Periactin,Merck Sharp and
Dohme,US,1961 | [Manufacturing Process]
(A) Preparation of 1-Methyl-4-Piperidyl-Magnesium Chloride: Magnesium
turnings (5.45 g, 0.22 g-atom) were placed in a 500 ml 3-necked flask
provided with a condenser, Hershberg stirrer and dropping funnel and
protected with a drying tube. An atmosphere of dry nitrogen was maintained
in 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 bromide
were added and after the reaction had subsided (formation of ethylmagnesium
bromide) a solution of 29.4 g (0.22 mol) of 4-chloro-1-methyl-piperidine in
dry tetrahydrofuran (total volume, 103 ml) was added dropwise at such a rate
that gentle reflux was maintained.
The solution of 4-chloro-1-methylpiperidine in tetrahydrofuran was dried over
calcium hydride at ice-bath temperature prior to use. When the addition of the
halide was complete the reaction mixture was refluxed with stirring for one
hour. In some subsequent experiments this period of refluxing was omitted
with no deleterious result.
The solution of 4-chloro-1-methylpiperidine in tetrahydrofuran was dried over
calcium hydride at ice-bath temperature prior to use. When the addition of the
halide was complete the reaction mixture was refluxed with stirring for one
hour. In some subsequent experiments this period of refluxing was omitted
with no deleterious result.
The solvent was evaporated from the combined benzene extracts to give 33.4
g of a clear light brown resin. Crystallization from an alcohol-water mixture
gave 19.5 g of 1-methyl-4-(5-hydroxy-5-dibenzo[a,e]cycloheptatrienyl)-
piperidine, MP 156° to 157°C. Two recrystallizations from alcohol-water
mixtures followed by two recrystallizations from benzene-hexane mixtures
gave 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 acetic
acid, 15 ml. The solution was saturated with dry hydrogen chloride with
external 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 solid
dissolved in the first 5 minutes of the heating period.
The reaction mixture was poured into 25 ml of water and the mixture made
strongly basic with 10N sodium hydroxide solution. The mixture was extracted
3 times with 50 ml portions of benzene, the combined extracts washed with
water and concentrated to a volume of approximately 50 ml. The solution was
saturated with dry hydrogen chloride and the white crystalline product
collected and dried. The yield of product, MP 251.6° to 252.6°C (dec.) was
2.5 g. Recrystallization from a mixture of absolute alcohol and absolute ether
gave a product, MP 252.6° to 253.6°C. A sample was analyzed after drying
for 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 warm
water 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 of
benzene and the extracts dried over sodium sulfate. Evaporation of the
benzene 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 water
gave 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. | [Clinical Use]
#N/A | [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]
Desiccate at -20°C | [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. |
| Safety Data | Back Directory | [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 |
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