Chlorpheniramine (Piriton; HSDB3032; HSDB-3032; Chlortrimeton; Deconamine; Neorestamin; NCIC-55265; NCIC55265; Chlo-Amine; Chlor-100; Chlor-Trimeton), is a potent and 1st-generation alkylamine-based histamine H1 receptor antagonist with anti-allergic effects. It inhibits histamine H1 receptor with an IC50 of 12 nM. Chlorpheniramine has been widely used for the prevention and treatment of the symptoms of allergic conditions such as rhinitis and urticaria.
Physicochemical Properties
| Molecular Formula | C17H20CLN |
| Exact Mass | 274.124 |
| CAS # | 132-22-9 |
| Related CAS # | Chlorpheniramine maleate;113-92-8;Chlorpheniramine-d6 maleate;1219806-45-7 |
| PubChem CID | 2725 |
| Appearance | OILY LIQUID |
| Melting Point | 25 °C (lit.) |
| LogP | 3.818 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 19 |
| Complexity | 249 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CN(C)CCC(C1=CC=C(C=C1)Cl)C2=CC=CC=N2 |
| InChi Key | SOYKEARSMXGVTM-UHFFFAOYSA-N |
| InChi Code | 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 |
| Chemical Name | 3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropan-1-amine |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | 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]. |
| ln Vivo | 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 Assay |
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 Protocol |
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. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Well absorbed in the gastrointestinal tract. STUDIES IN MAN & EXPTL ANIMALS INDICATE THAT (3)H-CHLORPHENIRAMINE MALEATE IS RAPIDLY & QUANT ABSORBED FROM GUT. ALTHOUGH PLASMA LEVELS OF TOTAL RADIOACTIVITY ARE PROLONGED, PLASMA T/2 OF CHLORPHENIRAMINE IS ONLY 12-15 HR IN MAN & 3 HR IN DOG. T/2 IN MAN IS ABOUT 3 TIMES LONGER THAN THERAPEUTIC EFFECT... The H1 antagonists are well absorbed from the GI tract. Following oral administration, peak plasma concn are achieved in 2 to 3 hr and effects usually last 4 to 6 hr; however, some of the drugs are much longer acting ... . /Histamine Antagonists: H1 Antagonists/ H1 blockers are among the many drugs that induce hepatic microsomal enzymes, and they may facilitate their own metabolism. /Histamine Antagonists: H1 Antagonists/ Metabolism / Metabolites Primarily hepatic via Cytochrome P450 (CYP450) enzymes. MAIN SITE OF METABOLIC TRANSFORMATION IS LIVER. /ANTIHISTAMINES/ Primarily hepatic via Cytochrome P450 (CYP450) enzymes. Half Life: 21-27 hours Biological Half-Life 21-27 hours IN MAN...PLASMA T/2 OF CHLORPHENIRAMINE IS...12-15 HR...ALTHOUGH PLASMA LEVELS OF TOTAL RADIOACTIVITY ARE PROLONGED... Elimination: 14 to 25 hours |
| Toxicity/Toxicokinetics |
Toxicity Summary Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Toxicity Data Oral LD50 (rat): 306 mg/kg Oral LD50 (mice): 130 mg/kg Oral LD50 (guinea pig): 198 mg/kg LD50: 306 mg/kg (Human) (A308) Interactions Concurrent use /of ototoxic medications/ with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo. /Antihistamines/ Concurrent use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended. /Antihistamines/ Concurrent use /with alcohol or other CNS depression-producing medications/ may potentiate the CNS depressant effects of either these medications or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications. /Antihistamines/ Anticholinergic effects may be potentiated when /anticholinergics or other medications with anticholinergic activity/ are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy. /Antihistamines/ Concurrent use /of other photosensitizing medications/ with antihistamines may cause additive photosensitizing effects. /Antihistamines/ |
| References |
[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. |
| Additional Infomation |
Therapeutic Uses Anti-Allergic Agents; Antipruritics; Histamine H1 Antagonists Antihistamines are indicated in the prophylactic and symptomatic treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis due to inhalant allergens and foods. /Antihistamines; Included in US product labeling/ Antihistamines are indicated for the symptomatic treatment of pruritus associated with allergic reactions and of mild, uncomplicated allergic skin manifestations of urticaria and angioedema, in dermatographism, and in urticaria associated with transfusions. /Antihistamines; Included in US product labeling/ Antihistamines are also used in the treatment of pruritus associated with pityriasis rosea. /Antihistamines; NOT included in US product labeling/ For more Therapeutic Uses (Complete) data for CHLORPHENIRAMINE (10 total), please visit the HSDB record page. Drug Warnings Use is not recommended in newborn or premature infants because this age group has an increased susceptibility to anticholinergic side effects, such as central nervous system excitation, and an increased tendency toward convulsions. A paradoxical reaction characterized by hyperexcitability may occur in children taking antihistamines. /Antihistamines/ Dizziness, sedation, confusion, and hypotension may be more likely to occur in geriatric patients taking antihistamines. Geriatric patients are especially susceptible to the anticholinergic side effects, such as dryness of mouth and urinary retention (especially in males), of the antihistamines. If these side effects occur and continue or are severe, medication should probably be discontinued. /Antihistamines/ Prolonged use of antihistamines ... may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort. /Antihistamines/ ANTIHISTAMINE DRUGS MAY BE OF SOME USE IN MINIMIZING SERUM REACTIONS BUT ARE OF NO THERAPEUTIC VALUE...& MAY EVEN POTENTIATE TOXIC ACTION OF VENOM... /ANTIHISTAMINES/ For more Drug Warnings (Complete) data for CHLORPHENIRAMINE (14 total), please visit the HSDB record page. Pharmacodynamics In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. |
Solubility Data
| Solubility (In Vitro) | 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 |
| Solubility (In Vivo) |
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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |