Plasmodium parasites are inhibited by chlorphenamine (IC50 values for D6 and Dd2 strains are 61.2 and 3.9 μM) [4]. Proton current in BV2 microglia is decreased by chlorphenamine (IC50: 43 μM)[1].

Leukocytes in peripheral blood are enhanced by chlorphenamine (50, 100, and 200 μg/kg; intramuscular injection; three times, one week apart) [2]. In BALB/c mice, ovalbumin-induced scratching activity is inhibited by oral chlorphenamine (10 mg/kg) [3].

Cell Viability Assay
Cell Types: Murine microglial BV2 cells[1].
Tested Concentrations: 100 μM
Incubation Duration: 5 min
Experimental Results: Inhibited proton currents with moderate potency.

Animal/Disease Models: SD (Sprague-Dawley) rats[2].
Doses: 50, 100 and 200 μg/kg
Route of Administration: Chlorpheniramine (50, 100 and 200 μg/kg; IM; 3 times, at intervals of 1 week)
Experimental Results: Enhanced white blood cells in the peripheral blood, mostly due to the increases of B cells and monocytes, but not T cells and NK cells.

Absorption, Distribution and Excretion
Absorbed well in the gastrointestinal tract.
Human and experimental animal studies have shown that (3) H-H-maleic acid chlorpheniramine can be rapidly and massively absorbed from the intestine. Despite prolonged total plasma radioactivity levels, the plasma half-life of chlorpheniramine is only 12-15 hours in humans and only 3 hours in dogs. The human half-life is approximately 3 times the duration of therapeutic effect…
H1 receptor antagonists are well absorbed in the gastrointestinal tract. After oral administration, peak plasma concentrations are reached within 2 to 3 hours, and the effect typically lasts 4 to 6 hours; however, some drugs have a longer duration of action… /Histamine antagonists: H1 receptor antagonists/
H1 receptor blockers are among many drugs that can induce hepatic microsomal enzymes, which may promote their own metabolism. /Histamine antagonists: H1 receptor antagonists/
Metabolism/Metabolites

Primarily metabolized in the liver by cytochrome P450 (CYP450) enzymes. The primary site of metabolic transformation is the liver. Antihistamines are mainly metabolized by hepatic cytochrome P450 (CYP450) enzymes. Half-life: 21-27 hours. In the human body… the plasma half-life of chlorpheniramine is… 12-15 hours… although the total radioactivity level in the plasma may be prolonged… Elimination: 14 to 25 hours.

Toxicity Summary
Chlorpheniramine binds to histamine H1 receptors. This blocks the action of endogenous histamine, thus temporarily relieving histamine-induced adverse symptoms. Toxicity Data
Oral LD50 (Rat): 306 mg/kg Oral LD50 (Mouse): 130 mg/kg Oral LD50 (Guinea Pig): 198 mg/kg LD50: 306 mg/kg (Human) (A308) Interactions Concomitant use of ototoxic drugs and antihistamines may mask ototoxic symptoms such as tinnitus, dizziness, or vertigo. /Antihistamines/ Monoamine oxidase (MAO) inhibitors may prolong and enhance the anticholinergic and central nervous system depressant effects of antihistamines; concomitant use is not recommended. /Antihistamines/
Concomitant use with alcohol or other central nervous system depressants may enhance the central nervous system depressant effects of these drugs or antihistamines; in addition, concomitant use with maprotiline or tricyclic antidepressants may enhance the anticholinergic effects of antihistamines or these drugs. /Antihistamines/
The anticholinergic effect may be enhanced when anticholinergic drugs or other drugs with anticholinergic activity are used in combination with antihistamines; patients should be advised to report gastrointestinal problems promptly, as concomitant use may lead to paralytic ileus. Antihistamines
Concomitant use of other photosensitizing drugs and antihistamines may produce additive photosensitizing effects.

[1]. Jiwon Kim, etal. Inhibitory effects of antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells. Eur J Pharmacol. 2017 Mar 5;798:122-128.

[2]. Kyung-Jin Jung, etal. Enhancement of B cell and monocyte populations in rats exposed to chlorpheniramine. Arch Pharm Res. 2012 Dec;35(12):2183-9.

[3]. Takano, N., I. Arai, and M. Kurachi, Analysis of the spontaneous scratching behavior by NC/Nga mice: a possible approach to evaluate antipruritics for subjects with atopic dermatitis. Eur J Pharmacol, 2003. 471(3): p. 223-8.

[4]. Design, synthesis, and evaluation of 10-N-substituted acridones as novel chemosensitizers in Plasmodium falciparum. Antimicrob Agents Chemother, 2007. 51(11): p. 4133-40.

Therapeutic Uses

Antihistamine; Antipruritic; Histamine H1 Receptor Antagonist
Antihistamines are indicated for the prevention and treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis caused by inhaled allergens and foods. /Antihistamines; included on the US product label/
Antihistamines are indicated for the treatment of itching associated with allergic reactions, as well as mild, uncomplicated allergic skin manifestations such as urticaria and angioedema, dermatographia, and transfusion-associated urticaria. /Antihistamines; included on the US product label/
Antihistamines are also used to treat itching associated with pityriasis rosea. /Antihistamines; not included on the US product label/
For more complete data on the therapeutic uses of chlorpheniramine (10 in total), please visit the HSDB record page.

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Drug Warning
This medication is not recommended for newborns or premature infants, as this age group is more sensitive to anticholinergic side effects (such as central nervous system excitation) and more prone to seizures. Children taking antihistamines may experience paradoxical reactions characterized by hyperexcitability. /Anthistamines/
Elderly patients are more likely to experience dizziness, sedation, confusion, and hypotension after taking antihistamines. Elderly patients are particularly susceptible to the anticholinergic side effects of antihistamines, such as dry mouth and urinary retention (especially in men). If these side effects occur and persist or are severe, discontinuation of the medication should be considered. /Anthistamines/
Prolonged use of antihistamines…may reduce or inhibit saliva production, leading to tooth decay, periodontal disease, oral candidiasis, and discomfort. /Antihistamines/
Antihistamines may help reduce serum reactions, but they have no therapeutic value…and may even enhance the toxicity of venom…/Antihistamines/
For more complete data on drug warnings for chlorpheniramine (14 in total), please visit the HSDB records page.

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Pharmacodynamics
In an allergic reaction, the allergen interacts with and cross-links with IgE antibodies on the surface of mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a series of complex reactions occur, ultimately leading to cell degranulation and the release of histamine (and other chemical mediators) from mast cells or basophils. After histamine release, it can react with local or systemic tissues via histamine receptors. Histamine acts on H1 receptors, causing itching, vasodilation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability, intensifying pain. Chlorpheniramine is an alkylamine histamine H1 receptor antagonist (more precisely, a histamine inverse agonist). It competes with histamine for normal H1 receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract. It can effectively and temporarily relieve symptoms such as sneezing, watery and itchy eyes, and runny nose caused by hay fever and other upper respiratory allergies.

C17H20CLN

274.124

132-22-9

Chlorpheniramine maleate;113-92-8;Chlorpheniramine-d6 maleate;1219806-45-7

2725

OILY LIQUID

25 °C (lit.)

3.818

0

2

5

19

249

0

CN(C)CCC(C1=CC=C(C=C1)Cl)C2=CC=CC=N2

SOYKEARSMXGVTM-UHFFFAOYSA-N

InChI=1S/C16H19ClN2/c1-19(2)12-10-15(16-5-3-4-11-18-16)13-6-8-14(17)9-7-13/h3-9,11,15H,10,12H2,1-2H3

3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropan-1-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)