Chlorphenamine (INN) or chlorpheniramine (USAN, former BAN), commonly marketed in the form of chlorpheniramine maleate (Chlorphen-12]), is a first-generation alkylamine antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. Its sedative effects are relatively weak compared to other first-generation antihistamines. Chlorphenamine is one of the most commonly used antihistamines in small-animal veterinary practice. Although not generally approved as an antidepressant or anti-anxiety medication, chlorphenamine appears to have these properties as well.
Chlorphenamine is part of a series of antihistamines including pheniramine (Naphcon) and its halogenated derivatives and others including fluorpheniramine, dexchlorpheniramine (Polaramine), brompheniramine (Dimetapp), dexbrompheniramine (Drixoral), deschlorpheniramine, dipheniramine (also known as triprolidine with the trade name Actifed), and iodopheniramine.
The halogenated alkyl amine antihistamines all exhibit optical isomerism, and chlorphenamine in the indicated products is racemic chlorphenamine maleate, whereas dexchlorpheniramine is the dextrorotary stereoisomer.
Serotonergic and norepinephrinergic effects
In addition to being an histamine H1 receptor antagonist, chlorphenamine has been shown to work as a serotonin-norepinephrine reuptake inhibitor or SNRI. A similar antihistamine, brompheniramine, led to the discovery of the SSRI zimelidine. Limited clinical evidence shows that it is comparable to several antidepressant medications in its ability to inhibit the reuptake of serotonin and also norepinephrine (noradrenaline). However, extensive clinical trials of its psychiatric properties in humans have not been conducted. It inhibits serotonin reuptake less than norepinephrine reuptake. however the literature is not consistent in this respect.
A study performed on Fischer 344/Brown Norway F1 hybrid rats showed that intraventricular administration of Chlorphenamine reduced fear-related behaviors and improved maze performance. It was also noted that long term administration of Chlorphenamine reduced age-related deficits in motor function.