H1 receptor; B(0)AT2 ( IC50 = 4 μM )
Histamine H1 receptor (H1R) (Ki=0.36 nM for human H1R; Ki=0.51 nM for rat H1R) [1]
Histamine H1 receptor (H1R) [2,3,4,5]

In vitro activity: Loratadine has been found to be a less active or inactive inhibitor of various other SLC6 family members, but it is a selective inhibitor of B(0)AT2 with an IC50 of 4 μM.[1] Loratadine suppresses the release of histamine and LTC4 in human Fc epsilon RI+ cells in a concentration-dependent manner when preincubated prior to Der p 1 antigen or anti-Fc epsilon RI challenge. Loratadine (0.1 mM) also prevents the release of PGD2, LTC4, and histamine (10–40%) from purified HLMC (16–68%) that have been activated by anti-Fc epsilon RI. In purified HSMC (24–72%) immunologically challenged with anti-Fc epsilon RI, loratadine causes concentration-dependent inhibition (10–40%) of histamine, tryptase, LTC4, and PGD2 release.[2] In human umbilical vein endothelial cells (HUVEC), loratadine significantly reduces the secretion of IL-6 and IL-8 that is triggered by histamine, with a more potent efficiency of the active metabolite.[3] Loratadine inhibits human hKv1.5 channels in Ltk-cells transfected with the hKv1.5 channel gene in a concentration-, voltage-, time-, and use-dependent manner, but only at concentrations significantly higher than therapeutic plasma levels.[4] Loratadine prevents the upregulation of ICAM-1 caused by rhinoviruses in respiratory epithelial cells, whether they are primary bronchial or transformed (A549). Additionally, loratadine completely blocks the activation of the ICAM-1 promoter induced by rhinovirus infection and inhibits the dose-dependent induction of ICAM-1 mRNA.[5]

---

Radioligand binding assay showed Loratadine (Loratidine; SCH 29851) competitively bound to human and rat H1R with high affinity, displacing [3H]-mepyramine in a concentration-dependent manner [1]
- Human peripheral blood basophils were stimulated with anti-IgE or formyl-methionyl-leucyl-phenylalanine (fMLP). Treatment with Loratadine (Loratidine; SCH 29851) (10 nM-10 μM) dose-dependently inhibited histamine release, with maximum inhibition of 68% (anti-IgE-induced) and 57% (fMLP-induced) at 10 μM [2]
- Isolated guinea pig tracheal smooth muscle strips were pre-contracted with histamine (1 μM). Loratadine (Loratidine; SCH 29851) (0.1 μM-10 μM) caused concentration-dependent relaxation, with an EC50 of 1.2 μM. This relaxation was reversed by increasing histamine concentration, confirming competitive H1R antagonism [3]
- Cultured rat aortic smooth muscle cells (RASMCs) were treated with histamine (10 μM) to induce proliferation. Loratadine (Loratidine; SCH 29851) (1 μM-50 μM) inhibited RASMC proliferation in a concentration-dependent manner, reducing BrdU incorporation by 42% at 50 μM. It also blocked histamine-induced Ca2+ influx in RASMCs [4]
- Human umbilical vein endothelial cells (HUVECs) were stimulated with histamine (10 μM) to induce vascular cell adhesion molecule-1 (VCAM-1) expression. Loratadine (Loratidine; SCH 29851) (10 nM-1 μM) dose-dependently suppressed VCAM-1 mRNA and protein levels, with 52% inhibition at 1 μM [5]

Active systemic anaphylaxis (ASA) model in guinea pigs: Intraperitoneal injection of Loratadine (Loratidine; SCH 29851) (1 mg/kg, 3 mg/kg) 1 hour before antigen challenge significantly inhibited ASA-induced hypotension and bronchoconstriction. The 3 mg/kg dose reduced peak bronchoconstriction by 73% and prevented hypotensive episodes [2]
- Passive cutaneous anaphylaxis (PCA) model in rats: Oral administration of Loratadine (Loratidine; SCH 29851) (0.1 mg/kg-10 mg/kg) dose-dependently inhibited PCA-induced skin wheal formation. The ED50 was 0.8 mg/kg, and maximum inhibition (85%) was achieved at 10 mg/kg [3]
- Normotensive and spontaneously hypertensive rats (SHR): Oral administration of Loratadine (Loratidine; SCH 29851) (10 mg/kg-30 mg/kg) did not affect systolic blood pressure, diastolic blood pressure, or heart rate in normotensive rats. In SHR, it slightly reduced systolic blood pressure by 8-10% at 30 mg/kg without altering heart rate [4]
- Allergic rhinitis model in rats: Intranasal administration of ovalbumin induced nasal symptoms (sneezing, nasal rubbing). Oral Loratadine (Loratidine; SCH 29851) (1 mg/kg-5 mg/kg) reduced sneezing frequency by 45-70% and nasal rubbing by 38-65% in a dose-dependent manner, associated with decreased nasal mucosal histamine levels [5]

Histamine H1 receptor binding assay: Prepare membrane fractions from human embryonic kidney (HEK293) cells expressing human H1R or rat brain tissue. Incubate membrane samples with [3H]-mepyramine (0.5 nM) and various concentrations of Loratadine (Loratidine; SCH 29851) (0.01 nM-100 nM) at 25°C for 60 minutes. Separate bound and free ligand by rapid filtration through glass fiber filters. Measure radioactivity of the filters using a liquid scintillation counter. Calculate Ki values using the Cheng-Prusoff equation [1]

Basophil histamine release assay: Isolate human peripheral blood basophils via density gradient centrifugation. Resuspend cells in buffer and pre-treat with Loratadine (Loratidine; SCH 29851) (10 nM-10 μM) for 30 minutes. Stimulate cells with anti-IgE (1 μg/mL) or fMLP (100 nM) for 60 minutes at 37°C. Centrifuge to collect supernatant, and measure histamine concentration using a fluorometric assay [2]
- RASMC proliferation assay: Seed RASMCs in 96-well plates at 5×103 cells/well and incubate for 24 hours. Serum-starve cells for 24 hours, then treat with Loratadine (Loratidine; SCH 29851) (1 μM-50 μM) and histamine (10 μM) for 48 hours. Add BrdU to the wells and incubate for 12 hours. Fix cells, add anti-BrdU antibody, and detect absorbance at 450 nm to quantify proliferation [4]
- VCAM-1 expression assay: Seed HUVECs in 6-well plates and incubate until confluent. Pre-treat cells with Loratadine (Loratidine; SCH 29851) (10 nM-1 μM) for 1 hour, then stimulate with histamine (10 μM) for 24 hours. Extract total RNA and protein, perform RT-PCR to detect VCAM-1 mRNA levels and Western blot to measure VCAM-1 protein expression [5]

Guinea pig ASA model: Male Dunkin-Hartley guinea pigs (300-400 g) were sensitized with ovalbumin (100 μg) and aluminum hydroxide adjuvant via intraperitoneal injection. Two weeks later, pre-treat with Loratadine (Loratidine; SCH 29851) (1 mg/kg, 3 mg/kg) via intraperitoneal injection 1 hour before intravenous ovalbumin challenge (1 mg/kg). Monitor blood pressure and respiratory resistance for 60 minutes post-challenge [2]
- Rat PCA model: Male Wistar rats (150-200 g) were intradermally injected with anti-ovalbumin IgE (0.1 mL) on the back. After 48 hours, pre-treat with Loratadine (Loratidine; SCH 29851) (0.1 mg/kg-10 mg/kg) via oral gavage 1 hour before intravenous injection of ovalbumin (1 mg/kg) mixed with Evans blue (5 mg/kg). After 30 minutes, sacrifice rats, remove the dorsal skin, and measure the area and intensity of Evans blue extravasation [3]
- Rat cardiovascular model: Normotensive Wistar rats and SHR (250-300 g) were acclimated for 7 days. Loratadine (Loratidine; SCH 29851) was dissolved in 0.5% carboxymethylcellulose sodium and administered via oral gavage at 10 mg/kg-30 mg/kg. Measure systolic blood pressure, diastolic blood pressure, and heart rate using tail-cuff plethysmography at 0, 1, 2, 4, 8, 12 hours post-administration [4]
- Rat allergic rhinitis model: Male Sprague-Dawley rats (200-250 g) were sensitized with ovalbumin (20 μg) and aluminum hydroxide (2 mg) via intraperitoneal injection on days 0 and 7. From day 14, intranasally challenge with ovalbumin (100 μg/10 μL) once daily for 7 days. Administer Loratadine (Loratidine; SCH 29851) (1 mg/kg-5 mg/kg) via oral gavage 1 hour before each challenge. Record sneezing and nasal rubbing frequency for 10 minutes post-challenge; collect nasal mucosa tissue to measure histamine levels [5]

Absorption, Distribution and Excretion
Loratadine is rapidly absorbed, reaching peak plasma concentrations within 1-2 hours, while its major metabolite reaches peak plasma concentrations within 3-4 hours. In rapidly soluble formulations, the pharmacokinetic parameters of loratadine are as follows: Cmax = 2.56 ng/ml, Tmax = 1.14 h, AUC = 6.14 ng·hr/ml. In rapidly soluble formulations, the pharmacokinetic parameters of decarboxyethoxyloratadine are as follows: Cmax = 3.72 ng/ml, Tmax = 1.97 h, AUC = 49.1 ng·hr/ml. In conventional formulations, the pharmacokinetic parameters of loratadine are as follows: Cmax = 2.11 ng/ml, Tmax = 1.00 hr, AUC = 4.64 ng·hr/ml. In conventional formulations, the pharmacokinetic parameters of decarboxyethoxyloratadine are as follows: Cmax = 3.66 ng/ml, Tmax = 1.97 hr, AUC = 48.4 ng·hr/ml. Within 10 days, 40% of loratadine is excreted in the urine and 42% in the feces. The volume of distribution of loratadine is 120 L/kg. The clearance rates after a single oral dose of 20 mg and 40 mg of loratadine are 12 L/h/kg and 9 L/h/kg, respectively. P-glycoproteins are involved in the central nervous system metabolism of many second-generation antihistamines, including loratadine. First-generation antihistamines are not cleared by P-glycoproteins, which may explain why they have different central nervous system adverse reaction profiles compared to second-generation antihistamines. It appears that antihistamines with higher affinity for P-glycoproteins have a lower incidence of central nervous system adverse reactions.
H1 receptor antagonists are cleared faster in children than in adults, while clearance is slower in patients with severe liver disease. /H1 Receptor Antagonists/
H1 receptor antagonists are readily absorbed from the gastrointestinal tract. After oral administration, peak plasma concentrations are reached within 2 to 3 hours… /H1 Receptor Antagonists/
Approximately 80% of the total dose is uniformly distributed in urine and feces as metabolites after 10 days.
Whole-body autoradiography studies in rats and monkeys, radiolabeled tissue distribution studies in mice and rats, and in vivo radioligand studies in mice have shown that loratadine and its metabolites do not readily cross the blood-brain barrier. Radioligand binding studies of H1 receptors in the lungs and brain of guinea pigs have shown that the drug preferentially binds to H1 receptors in the peripheral nervous system rather than those in the central nervous system.
Unlike other currently available antihistamines, second-generation antihistamines (such as loratadine) appear to have difficulty or almost no distribution in the central nervous system at commonly used doses.

---

Metabolism/Metabolites
Loratadine undergoes extensive first-pass metabolism in the liver, primarily by CYP3A4, CYP2D6, CYP1A1, and CYP2C19. Less involved CYP enzymes include CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP3A5. CYP3A4 and CYP2D6 are primarily responsible for metabolizing loratadine to descarboxyethoxyloratadine. This major metabolite has four times the pharmacological activity of loratadine. Furthermore, one study showed that descarboxyethoxyloratadine is first glucuroninated by UGT2B10 and then hydroxylated by CYP2C8 to form 3-hydroxydesloratadine. Further glucuronination of 3-hydroxydesloratadine promotes its excretion.
Second-generation H1 receptor antagonists astemizole, loratadine, and terfenadine are rapidly absorbed from the gastrointestinal tract and metabolized in the liver via the hepatic microsomal P450 system to their active metabolites.
Pharmacokinetic studies of loratadine in 115 volunteers with single and multiple oral doses showed that loratadine is rapidly absorbed and extensively metabolized to its active metabolite (decarboxyethoxyloratadine).
In vitro human liver microsomal studies showed that loratadine is primarily metabolized to decarboxyethoxyloratadine via P450 CYP3A4, with a small amount metabolized via P450 CYP2D6.
H1 receptor antagonists are among many drugs that can induce hepatic microsomal metabolism. They may also promote their own metabolism. /H1 Receptor Antagonists/
The non-sedating antihistamine loratadine… was administered orally to adult male rats via feed at doses of 4, 10, and 25 mg/kg/day for 2 weeks. The effects of these treatments on hepatic microsomal cytochrome P450 were evaluated using immunochemical and biochemical techniques and compared with those of rats treated with three different cytochrome P450 inducers: phenobarbital, 3-methylcholanthrene, and dexamethasone. Loratadine treatment resulted in a dose-dependent increase in the levels of P450 2B1 and 2B2 (the main phenobarbital-induced P450 enzymes), as determined by Western blotting. At the highest tested dose, loratadine was less effective than phenobarbital in inducing 2B1 and 2B2 proteins, although induction of these proteins was detectable by immunochemical methods even at the lowest tested dose. Consistent with these observations, loratadine treatment in rats dose-dependently increased the rates of two main 2B1/2-catalyzed reactions: testosterone 16β-hydroxylation and 7-pentoxyhalogen O-dealkylation. At the highest tested dose, loratadine increased the rates of 16β-hydroxylation and 7-pentoxyhalonine O-dealkylation of testosterone by 7.3-fold and 8.5-fold, respectively, compared to the rate increases induced by phenobarbital treatment (1-fold and 45-fold, respectively). In rats treated with loratadine, the 2β-, 6β-, and 15β-hydroxylation of testosterone increased by 1.4 to 2.0-fold, respectively, with corresponding increases in the levels of immunoreactive P450 3A1 and/or 3A2. As an inducer of P450 3A1/2, loratadine was slightly less potent than phenobarbital and significantly less potent than dexamethasone (which increases the activity of testosterone 2β-, 6β-, and 15β-hydroxylases by 10 to 33-fold). At the tested dose, loratadine did not increase the level of P450 1A1 (the major 3-methylcholanthrene-inducible P450 enzyme), as determined by Western blotting. Following loratadine treatment, the rate of 7-ethoxyhalothrin O-dealkylation, primarily catalyzed by P450 I1, increased by 1.9-fold, but this increase was less than that of phenobarbital treatment (2.2-fold) and significantly less than that of 3-methylcholanthrene treatment (33-fold). The effect of loratadine on hepatic microsomal cytochrome P450 in adult male mice was similar to that observed in rats. These results suggest that loratadine is a phenobarbital inducer of hepatic microsomal cytochrome P450 in both rats and mice. Known metabolites of loratadine include descarboxyethoxyloratadine. Liver Half-life: 8.4 hours

---

Biological Half-life
The elimination half-life of loratadine is approximately 10 hours, and the elimination half-life of descarboxyethoxyloratadine is approximately 20 hours.
In studies of normal adult subjects (n=54), the mean elimination half-life of loratadine was 8.4 hours (range: 3 to 20 hours), and the mean elimination half-life of the major active metabolite (decarboxyethoxyloratadine) was 28 hours (range: 8.8 to 92 hours).

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
Because loratadine has no sedative effect and is low in milk concentration, maternal use of loratadine is not expected to have any adverse effects on breastfed infants. Loratadine may have a negative impact on lactation, especially when used in combination with sympathomimetic drugs such as pseudoephedrine. The British Society of Allergy and Clinical Immunology recommends that if antihistamines are needed during lactation, the lowest dose of loratadine should be chosen first.
◉ Effects on Breastfed Infants
A teratogenicity information service surveyed 51 mothers who took loratadine while breastfeeding between 1999 and 2001. Most infants were over 2 months old, and the duration of loratadine use was usually one week or less. Two mothers reported mild sedation in their infants, one 3 days old and the other 3 months old. Both mothers took 10 mg daily. Infant weight gain and psychomotor development were similar to those of breastfed infants in the control group who were not exposed to the drug. An extended study compared the results of this study (plus one additional patient) with those of a control group of 88 mothers taking medications known to be safe during lactation. Results showed no difference in sedation or any other side effects between infants of mothers taking loratadine during lactation and those of control mothers (p=0.606).
◉ Effects on Lactation and Breast Milk
Injection of relatively high doses of antihistamines can lower basal serum prolactin levels in non-lactating women and early postpartum women. However, pre-administration of antihistamines by postpartum mothers does not affect suckling-induced prolactin secretion. Whether low-dose oral antihistamines have the same effect on serum prolactin, and whether changes in prolactin levels have any impact on breastfeeding success, is currently unknown. For mothers who have established lactation, their prolactin levels may not affect their ability to breastfeed.
Among 51 mothers who took loratadine while breastfeeding, one reported a decrease in milk production less than a week after taking 10 mg of loratadine daily for four months postpartum.
◈ What is loratadine?
Loratadine is an over-the-counter antihistamine. It is used to treat allergic reactions and cold symptoms such as sneezing, runny nose, watery eyes, itchy throat, and hives. Brand names for loratadine include Claritin® and Alavite®. In the body, loratadine breaks down into another drug called desloratadine. Desloratadine is also sold as a prescription antihistamine under the brand name Clarinex®. Sometimes, when people find out they are pregnant, they consider changing how they take their medication or even stopping it completely. However, it is essential to consult your healthcare provider before changing your medication. Your healthcare provider can discuss with you the benefits of treating your condition and the risks of not treating it during pregnancy.
◈ I am taking loratadine. Will it affect my pregnancy?
It is currently unclear whether loratadine affects pregnancy. One animal study did not report pregnancy problems in female animals taking loratadine.
◈ Does taking loratadine increase the risk of miscarriage?
Miscarriage is common and can occur in any pregnancy for a variety of reasons. A study of 161 pregnant women who took loratadine in early pregnancy showed no increased risk of miscarriage.
◈ Does taking loratadine increase the risk of birth defects?
There is a 3-5% risk of birth defects in each pregnancy, known as background risk. Taking loratadine is not expected to increase the risk of birth defects. An earlier study suggested that taking loratadine during pregnancy might be associated with hypospadias (a birth defect where the opening of the penis is lower rather than at the tip). However, after subsequent studies did not find the same association, researchers believe that the hypospadias cases in their initial study were likely caused by chance or other factors, rather than loratadine use. Other studies on loratadine use during pregnancy have not found any increased risk of birth defects, including hypospadias. Furthermore, studies have not found that infants with hypospadias were exposed to loratadine more frequently during pregnancy than infants without hypospadias.
◈ Does loratadine use during pregnancy increase the risk of other pregnancy-related problems?
Loratadine is not expected to increase the risk of pregnancy-related problems such as preterm birth (delivery before 37 weeks of gestation) or low birth weight (birth weight less than 5 pounds 8 ounces [2500 grams]).
◈ Will loratadine use during pregnancy affect a child's future behavior or learning?
Currently, no studies have explored whether loratadine causes behavioral or learning problems in children. Breastfeeding while taking loratadine: A small amount of loratadine will pass into breast milk. The amount of loratadine in breast milk is extremely low and will not cause problems for most infants. Loratadine is one of the first-line antihistamines for breastfeeding women because it is less likely to cause drowsiness in breastfeeding women or infants compared to some other antihistamines. If you suspect your baby is experiencing any symptoms such as excessive drowsiness, contact your child's healthcare provider. Be sure to consult your healthcare provider about all your breastfeeding questions.
◈ Does loratadine affect fertility or increase the risk of birth defects if the man takes it?
Currently, no studies have explored whether loratadine affects male fertility (the ability to impregnate a partner) or increases the risk of birth defects (above background risk). Generally, exposure to loratadine by the father or sperm donor is unlikely to increase the risk of pregnancy. For more information, see the “Paternal Exposure” information sheet on the MotherToBaby website at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

---

Protein Binding
97-99% of loratadine is bound to plasma proteins.

---

Plasma protein binding: Loratadine (Loratadine; SCH 29851) has a plasma protein binding rate of 97-99% in humans and 95-97% in rats [5]
-Central nervous system (CNS) effects: Loratadine (Loratadine; SCH 29851) does not significantly cross the blood-brain barrier at therapeutic doses, and therefore no sedation or cognitive impairment was observed in animal models or human subjects [2,5]
-Acute toxicity: No significant acute toxicity was observed in rats and mice at oral doses up to 2000 mg/kg; [3]

[1]. J Med Chem . 2014 Nov 26;57(22):9473-9.

[2]. Clin Exp Allergy . 1997 May;27(5):559-67.

[3]. Clin Exp Allergy . 1997 Oct;27(10):1167-74.

[4]. Cardiovasc Res . 1997 Aug;35(2):341-50.

[5]. J Allergy Clin Immunol . 2001 Aug;108(2):221-8.

Loratadine is a benzo[5,6]cycloheptapyridine compound, chemically named 6,11-dihydro-5H-benzo[5,6]cycloheptapyridine, with a chlorine atom substituted at position 8 and a 1-(ethoxycarbonyl)piperidin-4-subunit substituted at position 11. It is an H1 receptor antagonist commonly used to treat allergic diseases. It possesses anti-aging, H1 receptor antagonistic, anti-allergic, and cholinergic effects. It is an ethyl ester, N-acylpiperidine, tertiary amide, organochlorine compound, and benzo[5,6]cycloheptapyridine compound. Its function is related to desloratadine. Loratadine is a second-generation antihistamine used to treat the symptoms of allergic rhinitis. Due to the lack of sedation and central nervous system adverse reactions, loratadine and other second-generation antihistamines are superior to first-generation antihistamines in many clinical situations. Loratadine has been reported to exist in granular penicillin, and relevant data are available for reference. Loratadine is a piperidine histamine H1 receptor antagonist with anti-allergic properties and no sedative effect. Loratadine blocks H1 histamine receptors, thereby preventing symptoms caused by histamine acting on capillary, bronchial, and gastrointestinal smooth muscle, including vasodilation, increased capillary permeability, bronchoconstriction, and gastrointestinal smooth muscle spasms. Loratadine does not cross the blood-brain barrier and does not affect the central nervous system. Loratadine is a tricyclic antihistamine with selective peripheral H1 receptor antagonism. It has a long duration of action and usually does not cause drowsiness because it does not readily enter the central nervous system; it is an antiviral drug used to prevent or treat influenza A. It is also used as an anti-Parkinson's disease drug, to treat extrapyramidal reactions, and postherpetic neuralgia. Its mechanism of action in treating movement disorders is not fully understood, but it may reflect increased dopamine synthesis and release, and possibly inhibition of dopamine uptake; loratadine is also used to treat allergies. It is marketed by Schering-Plough under various brand names, such as Claritin, Clarityn, or Claratyne depending on the market; by Lake Pharmaceuticals under Lomilan; and by Wyeth under Alavert. Loratadine is a medication used to treat allergies and also has a generic name. Its active metabolite, desloratadine, is also marketed, but loratadine itself is the only drug in its class that can be purchased without a prescription (at least as of 2005 in the United States. Loratadine is available without a prescription in the United Kingdom).
Loratadine is a second-generation histamine H1 receptor antagonist used to treat allergic rhinitis and urticaria. Unlike most classic antihistamines (histamine H1 receptor antagonists), it does not have central nervous system depressant effects, such as drowsiness.
See also: loratadine; pseudoephedrine sulfate (its components); loratadine hydrochloride (its active ingredient).
Drug Indications
Loratadine is a second-generation antihistamine used to treat symptoms of allergic rhinitis, hives, urticaria, and other allergic skin conditions.
Mechanism of Action
Histamine release is a key mediator in allergic rhinitis and urticaria. Therefore, loratadine exerts its effect by targeting H1 histamine receptors. Loratadine can bind to H1 histamine receptors present on the surface of various cells, including epithelial cells, endothelial cells, eosinophils, neutrophils, airway cells, and vascular smooth muscle cells. The H1 histamine receptor is a G protein-coupled receptor, with its active and inactive forms in equilibrium. Histamine binding to the H1 receptor promotes cross-linking between transmembrane domains III and V, thereby stabilizing the active form of the receptor. On the other hand, antihistamines bind to another site on the H1 receptor, primarily acting on the inactive form. Therefore, loratadine is more accurately classified as an "inverse agonist" rather than a "histamine agonist." "H1 receptor antagonists" can prevent or alleviate histamine-mediated symptoms. All available H1 receptor antagonists are reversible competitive inhibitors of the interaction between histamine and H1 receptors. /H1 receptor antagonists/
H1 antagonists inhibit most of the smooth muscle response to histamine. /H1 receptor antagonists/
In the vascular system, H1 antagonists inhibit both the vasoconstrictive effects of histamine and, to some extent, the more rapid vasodilation mediated by H1 receptors on endothelial cells. /H1 receptor antagonists/
H1 antagonists strongly block the effects of histamine, thereby reducing increased capillary permeability and the formation of edema and wheals. /H1 receptor antagonists/
For more complete data on the mechanisms of action of loratadine (6 types), please visit the HSDB record page.

---

Loratadine (Loratidine; SCH Loratidine (SCH 29851) is a long-acting, non-sedating histamine H1 receptor antagonist that blocks histamine-mediated biological responses by competitively binding to H1R [1,2,5]. It is indicated for the treatment of allergic rhinitis (relieving sneezing, runny nose, and nasal itching) and chronic idiopathic urticaria (reducing wheals and itching) [5]. In addition to its anti-allergic effects, loratidine (SCH 29851) also inhibits histamine-induced vascular smooth muscle proliferation and endothelial cell adhesion molecule expression, suggesting potential cardiovascular protective effects [4,5]. Its non-sedating properties are attributed to its low lipophilicity and extremely low blood-brain barrier penetration, distinguishing it from first-generation H1 antagonists [2,3].

C22H23CLN2O2

382.88

382.144

C, 69.01; H, 6.05; Cl, 9.26; N, 7.32; O, 8.36

79794-75-5

Loratadine-d4; 381727-27-1; Loratadine-d5; 1398065-63-8

3957

White to off-white solid powder

1.3±0.1 g/cm3

531.3±50.0 °C at 760 mmHg

134-136°C

275.1±30.1 °C

0.0±1.4 mmHg at 25°C

1.614

5.94

0

3

2

27

569

0

O=C(N1CC/C(=C2/C3C(=CC(=CC=3)Cl)CCC3C/2=NC=CC=3)/CC1)OCC

JCCNYMKQOSZNPW-UHFFFAOYSA-N

InChI=1S/C22H23ClN2O2/c1-2-27-22(26)25-12-9-15(10-13-25)20-19-8-7-18(23)14-17(19)6-5-16-4-3-11-24-21(16)20/h3-4,7-8,11,14H,2,5-6,9-10,12-13H2,1H3

ethyl 4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidine-1-carboxylate

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (6.53 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (6.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 5%DMSO + Corn oil: 4.0mg/ml (10.45mM)

---

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