Description
Chlorpheniramine is a histamine H
1 receptor antagonist with an IC
75 value of 0.0016 μg/ml for reversal of histamine-induced spasms in isolated guinea pig ileum. It protects against intravenous histamine-induced death (PD
50 = 0.15 mg/kg) and delays induction of aerosolized histamine-induced coughing (ED
100sec = 0.44 mg/kg) in guinea pigs. Chlorpheniramine (20 mg/kg, i.p.) prevents histamine-induced passive cutaneous anaphylaxis (PCA) in rabbits. It also reduces respiratory resistance and hypersecretion of tracheobronchial fluid in a dog model of histamine-induced asthma. Formulations containing chlorpheniramine have been used in the treatment of seasonal allergies.
Chemical Properties
White Solid
Uses
(±)-Chlorpheniramine maleate salt has been used:
- as H1 receptor antagonist to determine the receptor function
- to block the effect of compound 48/80 on plasma IGF-I
- as a standard for fast sensing and determination by sequential injector coupled with potentiometer
Uses
An antagonist of the histamine H1-receptor
Definition
ChEBI: Chlorpheniramine maleate is an organic molecular entity.
brand name
Trimeton (Schering-Plough); Teldrin (GlaxoSmithKline).
General Description
Chlorpheniraminemaleate, (±)2-[p-chloro-α-[2-dimethylamino)ethyl]benzyl]pyridine bimaleate (Chlor-Trimeton), is a white crystallinepowder that is soluble in water (1:3.4), in alcohol(1:10), and in chloroform (1:10). It has a pKa of 9.2, and anaqueous solution has a pH between 4 and 5. Chlorination ofpheniramine in the para position of the phenyl ring increasespotency 10-fold with no appreciable change in toxicity.Most of the antihistaminic activity resides with thedextro isomer (see under “Dexchlorpheniramine Maleate” ).The usual dose is 2 to 4 mg 3 or 4 times a day. It has a halflifeof 12 to 15 hours.
General Description
Odorless white crystalline solid or white powder with a bitter taste. pH (2% aqueous solution) 5. pH (1% aqueous solution) 4-5.
Air & Water Reactions
Water soluble.
Reactivity Profile
A halogenated amine, ester. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. Esters react with acids to liberate heat along with alcohols and acids. Strong oxidizing acids may cause a vigorous reaction that is sufficiently exothermic to ignite the reaction products. Heat is also generated by the interaction of esters with caustic solutions. Flammable hydrogen is generated by mixing esters with alkali metals and hydrides.
Fire Hazard
Flash point data for Chlorpheniramine maleate are not available; however, Chlorpheniramine maleate is probably combustible.
Biochem/physiol Actions
Chlorpheniramine maleate (CPM) can prevent rhinitis and urticaria. It is used to cure several allergic conditions. This antihistamine is used in small-animal veterinary practices.
Safety Profile
Poison by ingestion, intravenous, and subcutaneous routes. Experimental reproductive effects. Used as an antihistamine. Mutation data reported. When heated to decomposition it emits very toxic fumes of Cland NOx.
Synthesis
The general procedure for the synthesis of 3-(4-chlorophenyl)-N,N-dimethyl-3-(pyridin-2-yl)propan-1-amine maleate from maleic acid and 3-(4-chlorophenyl)-N,N-dimethyl-3-(pyridin-2-yl)propan-1-amine was carried out as follows: in tetrahydrofuran solvent, 3-(4-chlorophenyl)-N,N-dimethyl-3-(pyridin-2-yl)propan -1-amine 260 g and sodium amide 95 g. The reaction temperature was maintained at 20~25°C and the reaction time was 20~25 hours. Subsequently, a toluene solution of N,N-dimethylchloroethane was slowly added dropwise, and the temperature was controlled to be 30~40°C during the dropwise addition. After the dropwise addition, the reaction system was warmed up to 40~45°C and the reaction was continued for 2 hours. After completion of the reaction, cooled to room temperature and washed the organic phase with water to neutral. The solvent was recovered to give 3-(4-chlorophenyl)-N,N-dimethyl-3-(pyridin-2-yl)propan-1-amine concentrate, which was concentrated by distillation under reduced pressure to obtain 270 g of product. To 500 g of anhydrous ethanol was added 130 g of maleic acid, stirred until completely dissolved, then 3-(4-chlorophenyl)-N,N-dimethyl-3-(pyridin-2-yl)propan-1-amine obtained above was added. After the addition was completed, stirring was continued for 30 minutes, followed by cooling to 0 to -2°C and maintaining this temperature for 2 hours. The reaction mixture was filtered to give crude maleic acid 3-(4-chlorophenyl)-N,N-dimethyl-3-(pyridin-2-yl)propan-1-amine salt 390 g. Finally, 350 g of the crude product was refined using 1.5 times volume of ethanol and ethyl chloroacetate.
Veterinary Drugs and Treatments
Antihistamines are used in veterinary medicine to reduce or help
prevent histamine
mediated adverse effects. Chlorpheniramine
is one the more commonly used antihistamines in the cat for the
treatment of pruritus. It may also be of benefit as a mild sedative in
small animals due to its CNS depressant effects.
Dosage forms
4 to 6 mg PO q4–6h. Maximum daily dose is 24 mg for adults
and children 12 years or older. Found frequently in combination with
acetaminophen and pseudoephedrine.
References
[1] Patent: CN106883167, 2017, A. Location in patent: Paragraph 0018; 0019
