Histamine H1 receptor. Diphenylpyraline acts as an H1 receptor antagonist, competing with histamine for H1-receptor sites on effector cells.

In mouse nucleus accumbens slices, diphenpyraline (10 μM) dramatically reduces dopamine uptake [2].

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In vitro, diphenylpyraline acts as an H1 receptor antagonist, blocking histamine-mediated responses. It effectively reduces allergic symptoms such as rhinitis, urticaria, and pruritus by blocking histamine-mediated responses. The compound has additional anticholinergic properties.

Intraperitoneal injection of 5–10 mg/kg diphenylpyrroline raises extracellular dopamine levels in the mouse nucleus accumbens by approximately 200 percent and causes mice to activate their locomotor system [2].

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Diphenylpyraline is used in vivo for the symptomatic relief of allergic conditions including rhinitis and hay fever, and in pruritic skin disorders. It is a sedating antihistamine with additional anticholinergic and sedative properties. The compound is administered orally as the hydrochloride salt.

In vitro H1 receptor binding assays for diphenylpyraline use radioligand binding techniques with membrane preparations from cells or tissues expressing the H1 receptor. Radiolabeled selective H1 antagonists such as [³H]-mepyramine are used as tracers. Competition binding experiments with varying concentrations of diphenylpyraline determine binding affinity (Ki). Non-specific binding is determined in the presence of excess unlabeled ligand.

In vitro cell-based assays for diphenylpyraline evaluate its antagonist activity at H1 receptors by measuring inhibition of histamine-induced responses. Cells expressing recombinant H1 receptors are loaded with calcium-sensitive dyes, stimulated with histamine to induce calcium mobilization, and the inhibition of this response by diphenylpyraline is measured. Alternative assays measure histamine-induced cAMP accumulation or other downstream signaling events.

Animal/Disease Models: C57BL/6 mice [2]
Doses: 5-10 mg/kg
Route of Administration: intraperitoneal (ip) injection
Experimental Results:It has psychostimulant properties.

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In vivo animal studies for diphenylpyraline typically use rodent models of allergic responses. The compound is administered orally or intraperitoneally, and endpoints include inhibition of histamine-induced vascular permeability (such as Evans blue dye extravasation), reduction in allergen-induced bronchoconstriction, or suppression of pruritus in scratching models. These studies confirm the compound's antihistaminic activity.

Absorption, Distribution and Excretion
Absorbed well after oral administration. Metabolism/Metabolites Liver

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Diphenylpyraline has a molecular weight of 281.18 g/mol (free base). As a first-generation antihistamine, it is orally bioavailable and distributes to the central nervous system due to its lipophilicity, accounting for its sedative properties. The compound is metabolized in the liver and excreted renally. Detailed pharmacokinetic parameters are established in the clinical pharmacology literature.

Protein Binding
99% Human Serum Albumin

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Diphenylpyraline is generally well-tolerated as an antihistamine. Common side effects include sedation, drowsiness, and anticholinergic effects such as dry mouth, blurred vision, and urinary retention. The compound may cause central nervous system depression and should not be used with alcohol or other CNS depressants. It is classified as a research-grade chemical.

[1]. Effects of the histamine H₁ receptor antagonist and benztropine analog diphenylpyraline on dopamine uptake, locomotion and reward.

[2]. Diphenylpyraline, a histamine H1 receptor antagonist, has psychostimulant properties.

Diphenylpyraline is a piperidine compound, a diphenyl methyl ether derivative of 1-methyl-4-hydroxypiperidine. It is a sedative antihistamine; its hydrochloride salt is used to relieve allergy symptoms, including rhinitis and hay fever, as well as to treat itchy skin conditions. It can also be used as an ingredient in combination preparations to relieve cough and common cold symptoms. It acts as both an H1 receptor antagonist and a cholinergic antagonist. It belongs to the piperidine class of compounds and is also a tertiary amine. Diphenylpyraline is an antihistamine. Antihistamines used to treat allergies act by competing with histamine for H1 receptor sites on effector cells. Antihistamines can prevent, but cannot reverse, reactions mediated solely by histamine. Antihistamines antagonize most of the pharmacological effects of histamine to varying degrees, including urticaria and pruritus. An allergen is a substance that causes an allergic reaction. See also: Diphenylpyraline hydrochloride (note moved to). Drug Indications Used to treat allergic rhinitis, hay fever, and allergic dermatitis. Mechanism of Action Antihistamines used to treat allergies, such as diphenylpyrrolidine hydrochloride, act by competing with histamine for H1 receptor sites on effector cells. This reduces the effect of histamine, thus temporarily relieving allergy symptoms. Pharmacodynamics Diphenylpyrrolidine hydrochloride is an antihistamine that prevents but does not reverse histamine-mediated reactions. Diphenylpyrrolidine antagonizes most of the pharmacological effects of histamine, including urticaria and pruritus. Additionally, diphenylpyrrolidine may have anticholinergic effects (like most antihistamines) and may therefore cause dryness of the nasal mucosa.

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Diphenylpyraline (CAS# 147-20-6) is a first-generation sedating antihistamine and H1 receptor antagonist. It is used for the symptomatic relief of allergic conditions including rhinitis, hay fever, and pruritic skin disorders. The compound has additional anticholinergic and sedative properties. It is a member of the piperidine class. It has not received FDA approval in modern times.

C19H23NO

281.392

281.178

147-20-6

132-18-3 (hydrochloride)

3103

White to off-white solid powder

1.08 g/cm3

378.7ºC at 760 mmHg

111.6ºC

6.18E-06mmHg at 25°C

1.587

3.824

0

2

4

21

268

0

OWQUZNMMYNAXSL-UHFFFAOYSA-N

InChI=1S/C19H23NO/c1-20-14-12-18(13-15-20)21-19(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18-19H,12-15H2,1H3

4-benzhydryloxy-1-methylpiperidine

AN1041; AN-1041; AN 1041

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)

DMSO : ~100 mg/mL (~355.38 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.88 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 (8.88 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
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 (8.88 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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 (Please use freshly prepared in vivo formulations for optimal results.)