Pheniramine

Absorption

The administration of 30.5 mg of free base pheniramine resulted in a Cmax of 173-294 ng/L with a Tmax of 1-2.5 h.

Toxicity

Case reports involving pheniramine overdosage mention the rare possibility of arrythmias, cutaneous eruptions, and rhabdomyolysis with acute kidney injury. The administration of activated charcoal effectively prevents the absorption of pheniramine as it largely adsorbs to the charcoal, therefore this may be of benefit in cases of overdose if provided early after ingestion.

Originator

Trimeton Maleate, Schering ,US,1948

The Uses of Pheniramine

Pheniramine is an antigripal drug. Also, it is derived from 2-Benzylpyridine (B288740), which is a benzylpyridine with antifungal properties. 2-Benzylpyridine is also used as a chromogenic reagent for micro determination of Molybednum.

Background

Pheniramine is a first-generation antihistamine in the alkylamine class, similar to brompheniramine and chlorpheniramine. It is used in some over-the-counter allergy as well as cold & flu products in combination with other drugs. Pheniramine's use as an anti-allergy medication has largely been supplanted by second-generation antihistamines such as cetirizine and loratadine.

Indications

Pheniramine is commonly used in over-the-counter products to treat seasonal allergies or cold and flu symptoms.

Definition

ChEBI: N,N-dimethyl-3-phenyl-3-(2-pyridinyl)-1-propanamine is a tertiary amino compound and a member of pyridines.

Manufacturing Process

According to US Patent 2,676,964: to 1.0 mol of potassium amide in 3 liters of liquid ammonia, is added 1.0 mol of 2-benzylpyridine. After 15 minutes, 1.1 mols of β-dimethylaminoethyl chloride are added. The ammonia is allowed to evaporate and the reaction product decomposed with water and ether extracted. The ether layer is dried over sodium sulfate and after evaporation the residue is distilled, giving the 3-phenyl-3-(2-pyridyl)-N,Ndimethylpropylamine, BP 139°-142°C/1-2 mm. The maleate is produced by reaction with maleic acid.

Therapeutic Function

Antihistaminic

Synthesis Reference(s)

The Journal of Organic Chemistry, 59, p. 7125, 1994 DOI: 10.1021/jo00102a044

Pharmacokinetics

Pheniramine acts as an antagonist to allergic symptoms stemming from inappropriate histamine release to reduce edema, itching, and redness. The same antihistamine effect also produces sedation by acting in the central nervous system.

Safety Profile

Poison by intravenous route. Human systemic effects by ingestion: central nervous system effects. When heated to decomposition it emits toxic fumes of NOx.

Enzyme inhibitor

This antihistamine (FWfree-base = 240.35 g/mol; CAS 86-21-5; insoluble in water; maleate and p-aminosalicylate salts are water-soluble), also known as N,N-dimethyl-g-phenyl-2-pyridinepropanamide, is more frequently abused than other antihistamines relative to its market share. One of the histamine H1 antagonists with little sedative action, pheniramine is often used in treatment of hay fever, rhinitis, allergic dermatoses, and pruritus. Target(s): H1 histamine receptor; and histamine Nmethyltransferase, mildly inhibited.

Metabolism

Pheniramine undergoes N-dealkylation to N-didesmethylpheniramine and N-desmethylpheniramine.