Histamine H1 receptor ( IC50 = 51 nM )

Desloratadine (1 mg/mL, 3 mg/mL, and 10 mg/mL) causes a long-lasting, dose-dependent mydriasis in guinea pigs in vivo.[1] Desloratadine has an ED50 of 0.15 mg/kg in mice, which prevents histamine-induced paw edema. For guinea pigs, desloratadine (ED50 = 0.9 μg) prevents the increase in microvascular permeability that occurs when the upper airway is challenged with histamine.[2] In conscious mice, desloratadine (5 mg/kg) inhibits oxotremorine-induced tremor by rupturing the blood-brain barrier. A shift in the dose-response curve to the right in the pithed rat indicates that desloratadine (1.0 mg/kg) significantly inhibits decreases in dP/dt induced by oxotremorine (0.00125 mg/kg, 0.0025 mg/kg, and 0.02 mg/kg). A shift in the dose-response curve to the right in the pithed rat indicates that desloratadine (1.0 mg/kg) significantly inhibits decreases in dP/dt induced by oxotremorine (0.00125 mg/kg, 0.0025 mg/kg, and 0.02 mg/kg). [5]

Absorption, Distribution and Excretion
Desloratadine administered orally for ten days to healthy volunteers as a 5 mg tablet once daily resulted in a mean Tmax of approximately 3 hours, a mean steady-state Cmax of 4 ng/ml, and a mean steady-state AUC of 56.9 ng\*hr/ml. A similar profile was observed using 10 ml of an oral solution containing 5 mg of desloratadine. Food was found not to affect desloratadine absorption.
Approximately 87% of a ¹⁴C-desloratadine dose was equally recovered in urine and feces as metabolic products.

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Metabolism / Metabolites
Desloratadine is metabolized to the active metabolite 3-hydroxydesloratadine, which is subsequently glucuronidated.
Desloratadine is a known human metabolite of Rupatadine and loratadine.

Route of Elimination: Desloratadine (a major metabolite of loratadine) is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuronidated. Approximately 87% of a 14C-desloratadine dose was equally recovered in urine and feces.
Half Life: 50 hours

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Biological Half-Life
Desloratadine has a mean plasma elimination half-life of approximately 27 hours.

Toxicity Summary
Like other H1-blockers, Desloratadine competes with free histamine for binding at H₁-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because of its expected low milk levels and lack of sedation and anticholinergic effects, maternal use of desloratadine is unlikely to affect a breastfed infant or milk production. Desloratadine might have a negative effect on lactation in combination with a sympathomimetic agent such as pseudoephedrine.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of antihistamines have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed

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Protein Binding
Desloratadine is bound approximately 82 to 87% to plasma proteins, while its active metabolite, 3-hydroxydesloratadine, is bound approximately 85 to 89%.

[1]. Eur J Pharmacol . 1999 Jun 18;374(2):249-54.

[2]. J Allergy Clin Immunol . 2001 Apr;107(4):751-62.

[3]. Clin Exp Allergy . 2001 Sep;31(9):1369-77.

[4]. Eur J Pharmacol . 2002 Aug 9;449(3):229-37.

[5]. BMC Pharmacol . 2005 Aug 18:5:13.

Desloratadine is loratadine in which the ethoxycarbonyl group attached to the piperidine ring is replaced by hydrogen. The major metabolite of loratidine, desloratadine is an antihistamine which is used for the symptomatic relief of allergic conditions including rhinitis and chronic urticaria. It does not readily enter the central nervous system, so does not cause drowsiness. It has a role as a H1-receptor antagonist, an anti-allergic agent, a cholinergic antagonist and a drug metabolite.
Desloratadine is a second generation, tricyclic antihistamine that which has a selective and peripheral H1-antagonist action. It is the active descarboethoxy metabolite of loratidine (a second generation histamine). Desloratidine has a long-lasting effect and does not cause drowsiness because it does not readily enter the central nervous system.
Desloratadine is a Histamine-1 Receptor Antagonist. The mechanism of action of desloratadine is as a Histamine H1 Receptor Antagonist.
Desloratadine has been reported in Bos taurus with data available.
Desloratadine is a long-acting piperidine derivate with selective H1 antihistaminergic and non-sedating properties. Desloratadine diminishes the typical histaminergic effects on H1-receptors in bronchial smooth muscle, capillaries and gastrointestinal smooth muscle, including vasodilation, bronchoconstriction, increased vascular permeability, pain, itching and spasmodic contractions of gastrointestinal smooth muscle. Desloratadine is used to provide symptomatic relieve of allergic symptoms.
Desloratadine is a second generation, tricyclic antihistamine that which has a selective and peripheral H1-antagonist action. It is the active descarboethoxy metabolite of loratidine (a second generation histamine). Desloratidine has a long-lasting effect and does not cause drowsiness because it does not readily enter the central nervous system.
See also: Desloratadine; pseudoephedrine sulfate (component of).

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Drug Indication
For the relief of symptoms of seasonal allergic rhinitis, perennial (non-seasonal) allergic rhinitis. Desloratidine is also used for the sympomatic treatment of pruritus and urticaria (hives) associated with chronic idiopathic urticaria.
FDA Label
Neoclarityn is indicated for the relief of symptoms associated with: allergic rhinitisurticaria
Aerius is indicated for the relief of symptoms associated with: allergic rhinitis; urticaria.
Azomyr is indicated for the relief of symptoms associated with: allergic rhinitis (see section 5. 1)urticaria (see section 5. 1)
Treatment of allergic rhinitis and urticaria.
Desloratadine ratiopharm is indicated in adults for the relief of symptoms associated with: allergic rhinitischronic idiopathic urticaria as initially diagnosed by a physician
Desloratadine Teva is indicated for the relief of symptoms associated with: allergic rhinitis; urticaria.
Dasselta is indicated for the relief of symptoms associated with: allergic rhinitis; urticaria.
Aerius is indicated for the relief of symptoms associated with: - allergic rhinitis (see section 5. 1)- urticaria (see section 5. 1)
Opulis is indicated for the relief of symptoms associated with: - allergic rhinitis (see section 5. 1)- urticaria (see section 5. 1)

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Mechanism of Action
Like other H1-blockers, Desloratadine competes with free histamine for binding at H₁-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine.

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Pharmacodynamics
Desloratadine is a long-acting second-generation H₁-receptor antagonist which has a selective and peripheral H1-antagonist action. Histamine is a chemical that causes many of the signs that are part of allergic reactions, such as the swelling of tissues. Histamine is released from histamine-storing cells (mast cells) and attaches to other cells that have receptors for histamine. The attachment of the histamine to the receptors causes the cell to be "activated," releasing other chemicals which produce the effects that we associate with allergies. Desloratadine blocks one type of receptor for histamine (the H1 receptor) and thus prevents activation of cells by histamine. Unlike most other antihistamines, Desloratadine does not enter the brain from the blood and, therefore, does not cause drowsiness.

C19H19CLN2

310.82

310.123

C, 73.42; H, 6.16; Cl, 11.41; N, 9.01

100643-71-8

Desloratadine-d4; 381727-29-3; Desloratadine-d9; 1795024-82-6; Desloratadine-3,3,5,5-d4; 2713301-38-1; Desloratadine-d5; 1020719-34-9

124087

White to off-white solid powder

1.2±0.1 g/cm3

467.9±45.0 °C at 760 mmHg

150-151°C

236.8±28.7 °C

0.0±1.2 mmHg at 25°C

1.626

6.77

1

2

0

22

425

0

ClC1C([H])=C([H])C2=C(C=1[H])C([H])([H])C([H])([H])C1C([H])=C([H])C([H])=NC=1/C/2=C1\C([H])([H])C([H])([H])N([H])C([H])([H])C\1([H])[H]

JAUOIFJMECXRGI-UHFFFAOYSA-N

InChI=1S/C19H19ClN2/c20-16-5-6-17-15(12-16)4-3-14-2-1-9-22-19(14)18(17)13-7-10-21-11-8-13/h1-2,5-6,9,12,21H,3-4,7-8,10-11H2

13-chloro-2-piperidin-4-ylidene-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene

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 (8.04 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.04 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.04 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.

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Solubility in Formulation 4: 30% Propylene glycol , 5% Tween 80 , 65% D5W: 30 mg/mL

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