129-03-3 Usage
Description
Cyproheptadine is a sedating antihistamine with antimuscarinic and calcium-channel blocking actions. It is known for its antianaphylactic activity, which is associated with its ability to slow down the release of histamine and other mediators from fat cells. Additionally, it is a serotonin receptor antagonist, making it useful in conditions such as vascular headache and anorexia.
Uses
Used in Allergy Treatment:
Cyproheptadine is used as an antihistaminic and antipruritic agent for the relief of allergic conditions, including rhinitis, conjunctivitis due to inhalant allergens and food, urticaria, angioedema, and pruritic skin disorders.
Used in Respiratory Conditions:
Cyproheptadine is used as a treatment for bronchial asthma attacks, allergic bronchitis, and rhinitis, helping to alleviate symptoms associated with these conditions.
Used in Anaphylactic Reactions:
Cyproheptadine is used as an adjuvant therapy for anaphylactic reactions, providing relief and support during severe allergic responses.
Used in Vascular Headache and Anorexia:
Due to its serotonin receptor antagonist properties, Cyproheptadine is used in the treatment of vascular headaches and anorexia, offering relief from these conditions.
Brand Names:
Some of the brand names for Cyproheptadine include 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, and Vimicon.
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.
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).
Check Digit Verification of cas no
The CAS Registry Mumber 129-03-3 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,2 and 9 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 129-03:
(5*1)+(4*2)+(3*9)+(2*0)+(1*3)=43
43 % 10 = 3
So 129-03-3 is a valid CAS Registry Number.
InChI:InChI=1/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
129-03-3Relevant articles and documents
Structure-activity relationships in the cyproheptadine series.
Engelhardt,Zell,Saari,Christy,Colton,Stone,Stavorski,Wenger,Ludden
, p. 829 - 835 (1965)
-
Synthesis and pharmacology of combined histamine H1-/H2-receptor antagonists containing diphenhydramine and cyproheptadine derivatives
Wolf, Cornelia,Schunack, Walter
, p. 87 - 94 (2007/10/02)
The classical histamine H1-receptor antagonists diphenhydramine (3a) and cyproheptadine (9) and their derivatives (3b-d, 10) were connected with a 2-guanidinothiazole containing structure (28) derived from the H2-receptor antagonist tiotidine in order to obtain combined H1/H2-receptor antagonists. The two moieties were not directly linked together, but were separated by a polymethylene spacer and a polar group (nitroethenediamine or urea). Thus 12 compounds were obtained that proved in vitro to possess high H1- and H2-receptor antagonist activity at the isolated guinea-pig ileum (H1) and the isolated guinea-pig right atrium (H2), respectively. The incorporation of the diphenhydramine as well as the cyproheptadine component provides high affinity to H1-receptors. The tricyclic cyproheptadine and its 10,11-dihydro derivative (30-32, 34), however, cause a decrease of H2-receptor antagonist potency compared to the diphenhydramines (29a-d, 33a-d). Using nitroethenediamine as the polar group is apparently more favourable to H1- and H2-receptor affinity as the urea function. All compounds elicit a dual mode of competitive and noncompetitive antagonism. Among the novel compounds the nitroethenediamines with 4-fluoro- or 4-methyl-substituted diphenhydramine as H1-receptor antagonist moiety (29c, d) display the most potent H1- and H2-receptor antagonist effects. The presented concept is a very promising way to combine H1- and H2-receptor antagonist properties in one molecule.
UNUSUAL REDUCTIONS INDUCED BY FORMIC ACID
Loughhead, David G.
, p. 5701 - 5702 (2007/10/02)
Treatment of xanthene carbinol 1a or xanthenylidene derivative 2a with refluxing formic acid unexpectedly gave dihydro compound 3a.Thioxanthene and acridine carbinols 1b and 1c and acridinylidene derivative 2c were also partially reduced when treated with formic acid.
