Olopatadine targets the histamine H1 receptor, a G protein-coupled receptor that mediates the effects of histamine in allergic reactions. It acts as a potent and selective antagonist, blocking histamine-induced vasodilation, increased vascular permeability, and smooth muscle contraction. Additionally, olopatadine stabilizes mast cells, preventing the release of histamine and other inflammatory mediators such as leukotrienes and cytokines. This dual mechanism of action contributes to its anti-allergic and anti-inflammatory effects.

Olopatadine dramatically lowers the upregulation of ICAM (intercellular adhesion molecule)-1 in vitro induced by mast cell supernatant and suppresses the production of TNF-α from human conjunctival mast cells when exposed to anti-IgE antibodies [2].
In vitro, olopatadine demonstrates high affinity for the histamine H1 receptor with a Ki of 2.6 nM. It inhibits histamine-induced contractions in isolated guinea pig ileum. It also inhibits the release of histamine from mast cells and reduces the production of pro-inflammatory cytokines. In cell-based assays, olopatadine shows potent inhibition of allergic inflammatory responses. These in vitro activities confirm its profile as a potent antihistamine and mast cell stabilizer.

In vivo, olopatadine has demonstrated efficacy in animal models of allergic conjunctivitis and allergic rhinitis. It reduces histamine-induced vascular permeability and inhibits allergic reactions in the eye and nose. In guinea pig models, it inhibits antigen-induced conjunctivitis and nasal hyperresponsiveness. These in vivo findings support its clinical use for the treatment of allergic conjunctivitis and allergic rhinitis, where it provides rapid and effective relief of symptoms.

The in vitro receptor binding assay for olopatadine typically involves radioligand displacement studies using membrane preparations from cells expressing the human H1 receptor. The compound's affinity (Ki) is determined by measuring its ability to displace a specific radiolabeled ligand from the receptor. These cell-free assays provide a direct measure of the compound's binding affinity for the H1 receptor, confirming its potent and selective antagonist profile.

In vitro cellular assays for olopatadine assess its functional antagonism at the H1 receptor and its mast cell stabilizing activity. Cells expressing the H1 receptor are stimulated with histamine, and the compound's ability to inhibit downstream signaling, such as calcium flux, is measured. Mast cell stabilization is assessed by measuring the inhibition of histamine release from mast cells stimulated with IgE and antigen. These assays demonstrate the compound's dual mechanism of action.

In vivo animal studies for olopatadine have been conducted in guinea pig and rat models of allergic conjunctivitis and allergic rhinitis. Allergic reactions are induced by antigen challenge, and olopatadine is administered topically or systemically. Endpoints include vascular permeability, inflammatory cell infiltration, and clinical signs such as itching and redness. These studies demonstrate the compound's efficacy in reducing allergic responses in vivo.

Absorption, Distribution and Excretion
In healthy subjects, after ocular administration of olopatadine, the peak plasma concentration (Cmax) was 1.6 ± 0.9 ng/mL, reached approximately 2.0 hours later. The AUC was 9.7 ± 4.4 ng·h/mL. The mean absolute bioavailability of olopatadine after intranasal administration was approximately 57%. In healthy subjects, after intranasal administration twice daily, the steady-state peak plasma concentration (Cmax) was 6.0 ± 8.99 ng/mL, reached between 30 minutes and 1 hour after administration. The mean AUC was 66.0 ± 26.8 ng·h/mL. In patients with seasonal allergic rhinitis, the steady-state peak plasma concentration (Cmax) was 23.3 ± 6.2 ng/mL, reached between 15 minutes and 2 hours after administration, with a mean AUC of 78.0 ± 13.9 ng·h/mL. Olopatadine is primarily excreted in the urine. Following oral administration, approximately 70% and 17% of the total dose are excreted in the urine and feces, respectively. In an open-label study involving healthy Chinese subjects, the mean apparent volume of distribution after oral administration of olopatadine was 133.83 L. In another open-label study involving healthy Chinese subjects, the mean apparent oral clearance (CL/F) after oral administration of olopatadine was 23.45 L/h. Metabolites/Metabolites Olopatadine is primarily metabolized in the liver, but to a limited extent. According to oral pharmacokinetic studies, at least six circulating metabolites exist in human plasma. Following topical ocular administration of olopatadine, it is metabolized to olopatadine N-oxide under the catalysis of flavin monooxygenases (FMOs) 1 and 3, and was detected in the plasma of half of the patients at a concentration less than 10% of the total plasma volume 4 hours after administration. Olopatadine monodemethyl (or N-demethyl olopatadine) is metabolized by CYP3A4 and can be detected at very low concentrations in vivo. Known metabolites of olopatadine include N-monodemethyl olopatadine. Both the monodemethyl metabolite and the N-oxide metabolite are detected at low concentrations in urine. Elimination route: Primarily excreted via the kidneys. Half-life: 3 hours. Following ocular administration, the elimination half-life of olopatadine is 3.4 ± 1.2 hours. Oral pharmacokinetic studies indicate an elimination half-life of 8 to 12 hours.
Olopatadine is rapidly absorbed after oral and topical administration. It has an oral bioavailability of approximately 50% and a plasma half-life of approximately 8-12 hours. It is primarily excreted unchanged in the urine. For ophthalmic and intranasal administration, systemic absorption is minimal, contributing to its favorable safety profile. The compound's pharmacokinetic properties support its use as a once- or twice-daily medication for allergic conditions.

Toxicity Summary
Olopatadine is a selective histamine H1 receptor antagonist that binds to histamine H1 receptors. This blocks the action of endogenous histamine, thereby temporarily relieving histamine-induced adverse symptoms. Olopatadine has no effect on alpha-adrenergic receptors, dopamine receptors, or muscarinic type 1 and 2 receptors.

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Effects During Pregnancy and Lactation
◉ Use During Lactation
Due to limited absorption through the eyes, lopatadine is not expected to have any adverse effects on breastfed infants. To significantly reduce the amount of medication that enters breast milk after using eye drops, press the tear duct near the corner of the eye for at least 1 minute, then wipe away any excess medication with absorbent tissue.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Breastfeeding and Breast Milk
No published information found as of the revision date.

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Protein Binding
Approximately 55% of olopatadine binds to human serum proteins, with serum albumin being the primary binding protein.

Olopatadine has a well-established safety profile based on extensive clinical use. Common adverse effects include mild irritation at the site of application (eye or nose) and headache. Systemic side effects are rare due to the low systemic absorption of the ophthalmic and nasal formulations. It is generally well-tolerated and has a low risk of sedation compared to first-generation antihistamines. Its safety profile has been established in numerous clinical studies.

[1]. Topical Olopatadine in the Treatment of Allergic Conjunctivitis: A Systematic Review and Meta-analysis. Ocul Immunol Inflamm. 2017 Oct;25(5):663-677.

[2]. Olopatadine: a drug for allergic conjunctivitis targeting the mast cell. Expert Opin Pharmacother. 2010 Apr;11(6):969-81.

Pharmacodynamics
Inflammatory responses induced by various stimuli are mediated by endogenous mediators and other pro-inflammatory factors. Histamine receptor activation and mast cell degranulation are the main mechanisms leading to inflammatory responses such as itchy eyes, congestion, conjunctival edema, eyelid swelling, and tearing in seasonal allergic conjunctivitis. Olopatadine is an anti-allergic molecule and mast cell stabilizer that inhibits type I immediate hypersensitivity reactions in vivo. Olopatadine alleviates allergic and inflammatory symptoms at various administration sites, including the eyes and nose, by blocking the action of histamine. It has shown antihistamine activity in isolated tissues, animal models, and humans. Olopatadine has also shown dose-dependent inhibition of histamine release from immune-stimulated rat basophilic leukemia cells and human conjunctival mast cells (in vitro experiments). Olopatadine has a relatively rapid onset of action and a long duration of action, exerting its antihistamine effect from 5 minutes to 24 hours after administration. Although olopatadine is a non-sedating antihistamine, drowsiness has been reported in some patients using nasal olopatadine in clinical trials. Transient blurred vision or other visual disturbances have been observed after ophthalmic administration. Olopatadine has negligible effects on alpha-adrenergic receptors, dopamine receptors, muscarinic receptors type 1 and 2, and serotonin receptors. No QT interval prolongation was observed after intranasal administration of olopatadine in clinical trials.
Olopatadine is an FDA-approved medication for the treatment of allergic conjunctivitis (ophthalmic solution) and allergic rhinitis (nasal spray). It is a potent and selective H1 receptor antagonist with mast cell stabilizing properties. Its rapid onset of action and favorable safety profile make it a widely used treatment for allergic conditions. It is available by prescription and over-the-counter in some countries. It is also used in research as a reference compound for studying allergic inflammation.

337.41222

337.167

113806-05-6

Olopatadine hydrochloride;140462-76-6;Olopatadine-d6;1231979-85-3

5281071

Typically exists as solid at room temperature

1.2±0.1 g/cm3

523.0±50.0 °C at 760 mmHg

248 °C

270.1±30.1 °C

0.0±1.4 mmHg at 25°C

1.641

3.14

1

4

5

25

488

0

CN(C)CC/C=C\1/C2=CC=CC=C2COC3=C1C=C(C=C3)CC(=O)O

JBIMVDZLSHOPLA-LSCVHKIXSA-N

InChI=1S/C21H23NO3/c1-22(2)11-5-8-18-17-7-4-3-6-16(17)14-25-20-10-9-15(12-19(18)20)13-21(23)24/h3-4,6-10,12H,5,11,13-14H2,1-2H3,(H,23,24)/b18-8-

2-[(11Z)-11-[3-(dimethylamino)propylidene]-6H-benzo[c][1]benzoxepin-2-yl]acetic acid

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.)