Chlorphenamine (chlorpheniramine) maleate is an alkylamine H₁ receptor antagonist. Chlorpheniramine is among the most potent and most selective H₁ antagonist (relative selectivity for H₁:H₂ receptors is 15000:1). In addition to being histamine H₁ receptor antagonist, chlorphenamine has been shown to work as a serotonin-norepinephrine reuptake inhibitor(SNRI). It has less sedative effect and is not likely to produce intense drowsiness.

Pharmacokinetics

Chlorphenamine  maleate is well absorbed after oral administration, but undergoes some degree of first pass metabolism in liver. It is well distributed in body, metabolised mainly in liver and excreted both as metabolites and unchanged drug in the urine.

Mechanism of Action

The H₁ receptor antagonists do not influence formation or release of histamine, but they antagonise actions of histamine at H₁-receptor sites. These drugs block all actions of histamine except for those mediated solely by H₂-receptors. In recent years, it has been shown that these drugs are actually H₁-receptor inverse agonist rather than H₁-receptor antagonists as they stabilise the H₁-receptor in inactive state. However, the older concept still prevails and even today they are commonly called H₁-receptor antagonists. In addition to H₁ blocking action , many of these drugs tend to block muscarinic receptors and few drugs also antagonise adrenergic or serotonin receptors.  

Clinical Uses

Chlorphenamine maleate is one of the most commonly used antihistamines in small-animal veterinary practice. It is commonly used as premedication for drugs which may induce an anaphylactic reaction(e.g. cytotoxic drugs), to control pruritis in allergic skin disorders, and in behavior modification programmes. Although not generally approved as an antidepressant or anti-anxiety medication, chlorphenamine appears to have these properties as well. Chlorphenamine is often combined with phenylpropanolamine to form an allergy medication with both antihistamine and decongestant properties. It is also combined with cough suppressant dextromethorphan to produce antiallergic and antitussive effects.

Adverse effects

Important adverse effects of chlorphenamine include CNS depression and GI disturbances.