Cyproheptadine Chemical Properties

Melting point:

112.3-113.3°

Boiling point:

419.7°C (rough estimate)

Density 

0.9917 (rough estimate)

refractive index 

1.8240 (estimate)

storage temp. 

Store at -20°C

pka

pKa 8.87 (Uncertain)

color 

Crystals from EtOH (aq)

Water Solubility 

317.6ug/L(22.5 ºC)

CAS DataBase Reference

129-03-3(CAS DataBase Reference)

NIST Chemistry Reference

Cyproheptadine(129-03-3)

Safety Information

HS Code 

29143900

Hazardous Substances Data

129-03-3(Hazardous Substances Data)

Toxicity

LD50 orl-rat: 295 mg/kg 27ZQAG -,69,72

MSDS

• Language:English Provider:Cyproheptadine

Cyproheptadine Usage And Synthesis

Description

Cyproheptadine has antianaphylactic activity that is associated with its ability to slow down the release of histamine and other mediators from fat cells.

Originator

Periactin,Merck Sharp and Dohme,US,1961

Uses

It is mainly used for treating bronchial asthma attacks, allergic bronchitis, rhinitis, and allergic skin reactions as well as in adjuvant therapy for anaphylactic reactions. Synonyms of this drug are periactin and vimicon.

Uses

Antihistaminic; antipruritic.

Definition

ChEBI: The product resulting from the formal oxidative coupling of position 5 of 5H-dibenzo[a,d]cycloheptene with position 4 of 1-methylpiperidine resulting in the formation of a double bond between the two fragments. t is a sedating antihistamine with antimuscarinic and calcium-channel blocking actions. It is used (particularly as the hydrochloride sesquihydrate) for the relief of allergic conditions including rhinitis, conjunctivitis due to inhalant allergens and food , urticaria and angioedema, and in pruritic skin disorders. Unlike other antihistamines, it is also a seratonin receptor antagonist, making it useful in conditions such as vascular headache and anorexia.

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);Anarexal;Antegan;Apeplus;Brantina;Brantine;Carnigol;Carpantin;Ciplactin;Cipractin;Cipro n;Ciprocort;Cyrasarl;Estialim;Histatets;Ifrasarl;Kontrast u;Naidoretico;Nurdelin;Nuttriben;Oractine;Orexigen;Periactol;Perideca;Pranzo;Reparal carnitina;Siglatan;Sigloton;Sipraktin;Siprodin;Vimicon.

Therapeutic Function

Antipruritic, Antihistaminic, Appetite stimulant

World Health Organization (WHO)

Cyproheptadine, an antihistamine with anticholinergic and serotonin-antagonist properties, was introduced in 1961 for the symptomatic relief of allergy and was subsequently used as an appetite stimulant. In 1982 the drug was prohibited in Bangladesh because of its misuse as an appetite stimulant due to inappropriate promotion. Cyproheptadine remains widely available and the current marketing policy of the major manufacturer requires that it should be used as an appetite stimulant only under the supervision of a physician who should be assured that adequate food is available.

Safety Profile

Poison by ingestion, intraperitoneal, subcutaneous and intravenous routes. Experimental teratogenic and reproductive effects. When heated to decomposition it emits toxic fumes of NOx.

Synthesis

Cyproheptadine, 4-(dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine (16.1.21), is synthesized by reacting 1-methyl-4-magnesiumchloropiperidine with 5H-dibeno[a,d]cycloheptene-5-one, which forms carbinol (16.1.20), the dehydration of which in an acidic medium leads to the formation of cyproheptadine (16.1.21).

Cyproheptadine(129-03-3)Related Product Information

• Mepiquat chloride
• Haloperidol
• PHENCYCLIDINE-D5 HYDROCHLORIDE
• Diphenoxylate
• CYPROHEPTADINE HCL
• Cyproheptadine hydrochloride sesquihydrate
• CYPROHEPTADINE HCL,CYPROHEPTADINE HCL BP
• Cyproheptadine Related Compound A
• CYPROHEPTADINE N-OXIDE
• cyproheptadine 10,11-epoxide
• Cyproheptadine
• CYPROHEPTADINE HYDROCHLORIDE SESQUIHYDRATE MM(CRM STANDARD)
• CYPROHEPTADINE A-N-OXIDE
• cyproheptadine glucuronide
• CYPROHEPTADINE HYDROCHLORIDE IMP. B (EP): 5H-DIBENZO[A,D]CYCLOHEPTEN-5-ONE (DIBENZOSUBERENONE)
• CYPROHEPTADINE B-N-OXIDE
• CYPROHEPTADINE HYDROCHLORIDE SESQUIHYDRATE IMP. B (EP): DI BENZOSUBERENONE MM(CRM STANDARD)