Description

Neurological Disease

Description

Chlorpheniramine (Chlorpheniramine maleate, Chlorphenamine) is a histamine H1 receptor antagonist with IC50 of 12 nM.

Targets

IC₅₀

In Vitro

Chlorpheniramine inhibits the [³H]mepyramine binding to the histamine H1 receptor in guinea pig cortex with IC50 of 8.8 nM. ^[2] Chlorpheniramine inhibits the proliferation of MCF-7, MDA-MB 231, and Ehrlich cells in a dose-response manner, and significantly reduces the ornithine decarboxylase mRNA translation by 50%-70% at the 250 μM. ^[3] Chlorpheniramine displaces of [³H]pyrilamine from human histamine receptor subtype 1 expressed in CHO cells with IC50 of 66 nM. Chlorpheniramine displays antimalarial activity against CQS strain (D6) and MDR strain (Dd2) of P. falciparum with IC50 of 61.2 uM and 3.9 uM, respectively. Chlorpheniramine displays cytotoxicity against the proliferation of concanavalin A-induced murine splenic lymphocytes with IC50 of 33.4 μM. ^[4] Chlorpheniramine treatment in human salivary gland cells more significantly inhibits the histamine-induced [Ca²⁺]_i increase in a concentration-dependent manner with IC50 of 128 nM than that of carbachol-induced [Ca²⁺]_i increase with an IC50 of 43.9 μM. ^[5]

In Vivo

Oral administration of Chlorpheniramine inhibits histamine-induced mortality in guinea pigs with an ED50 of 0.17 mg/kg. ^[1] Oral administration of Chlorpheniramine (10 mg/kg) significantly inhibits short-duration scratching in BALB/c mice stimulated by ovalbumin active cutaneous anaphylaxis and in ICR mice subcutaneously injected with histamine, but not long-duration scratching seen in NC/Nga mice, in contrast to that of dexamethasone or tacrolimus. ^[6] Administration of Chlorpheniramine (20 mg/kg) significantly abolishes the increase in REM sleep in rats induced by immobilization stress due to the blockage of the histaminergic and cholinergic mechanisms generating REM sleep. ^[7]

Clinical Trials

A Phase III study to evaluate the efficacy and safety of a fixed combination of paracetamol, phenylephrine and Chlorpheniramine in symptomatic treatment of common cold and flu-like illness in adults has been completed.

Features

H1-Antihistaminic Activity

The segments (1 cm) of isolated ileum from guinea pigs are suspended in an organ bath containing Tyrode solution (ventilation, 32 °C). The contractile responses to histamine (0.54 μM) are measured with an isotonic transducer. A set concentration of Chlorpheniramine is added in the organ bath 5 minutes before the addition of histamine. IC50 value of Chlorpheniramine is calculated by the probit methond.

Cell Lines

MCF-7, MDA-MB 231, and Ehrlich

Concentrations

Dissolved in water, final concentrations ~500 μM

Incubation Time

48 hours

Methods

Cells are exposed to various concentrations of Chlorpheniramine for 48 hours. Cells are washed, detached, and counted with a Coulter counter for the determination of cell growth.

Animal Models

Male NC/Nga mice, male ICR mice and female BALB/c mice with atopic dermatitis

Formulation

Suspended in 1% (v/v) Tween 80

Doses

10 mg/kg

Administration

Orally