H1 Receptor 1.01 mM (IC50)

In order to extend the duration of antihistaminic effects and delay metabolic time, pheniramine inhibits CYP2D6, a particular P450-isozyme[1]. By blocking histamine with an IC50 value of 1.01 mM, pheniramine prevents Ca2+ influx into BC3H-1 cells and controls the activity of the Ca2+ transmembrane in cells[2].In human T-cell acute lymphoblastic leukemia cell lines, pheniramine (0.5, 1.0 mM; 24 h) induces cell apoptosis[3]. The time-dependent inhibition of cell proliferation by pheniramine (1 μM-1 mM; 12-48 h) had inhibitory concentration IC50s of 550 μM for CCRF-CEM cells and 420 μM for Jurkat cells, respectively[3].

In rats, pheniramine (1.75 μM) causes spinal block and a local anesthetic effect[4].

Apoptosis Analysis [3]
Cell Types: Human T-cell acute lymphoblastic leukemia
Cell Types: CCRF-CEM and Jurkat ALL
Tested Concentrations: 0.5, 1.0 mM
Incubation Duration: 24 hrs (hours)
Experimental Results: Induced cells apoptosis with chromatin condenses and marginalizes, and nuclear debris spread into the cytoplasm.

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Cell Viability Assay[3]
Cell Types: Human T-cell acute lymphoblastic leukemia
Cell Types: CCRF-CEM and Jurkat ALL
Tested Concentrations: 1 μM-1 mM
Incubation Duration: 12, 24, 48 hrs (hours)
Experimental Results: Inhibited cell proliferation and survival in a time- and dose-dependent manner.

Animal/Disease Models: Sprague–Dawley rats (300-350 g ; male)[4]
Doses: 0.30, 0.60, 0.90, 1.50, 1.75 μM
Route of Administration: Intrathecal injection; one time
Experimental Results: Resulted the spinal block and displayed dose-dependent effect. demonstrated 100% blockades in motor function, proprioception, and nociception , with full recovery duration of action about 41, 56, and 88 min, respectively, at 1.75 μM.

Absorption, Distribution and Excretion
Following intravenous injection of 30.5 mg of the free base beniramine, the peak plasma concentration (Cmax) ranges from 173 to 294 ng/L, with a time to peak concentration (Tmax) of 1 to 2.5 h. Beniramine is primarily eliminated through metabolism and renal excretion. Approximately 24.3% of beniramine remains in its original form in urine. Metabolism/Metabolites Beniramine undergoes N-dealkylation to produce N-didesmethylbeniramine and N-desmethylbeniramine. Biological Half-Life The terminal half-life of intravenously administered beniramine is 8–17 h.

Effects During Pregnancy and Lactation
◈ What is Benniralamine? Benniralamine is an antihistamine approved for treating allergy symptoms such as nasal congestion and swollen eyes. It has also been used to treat dermatitis (skin inflammation) and motion sickness. Benniralamine may be listed as benniralamine maleate on the drug label. Benniralamine is available in over-the-counter combination medications. Sometimes, when people find out they are pregnant, they consider changing how they take their medication or even stopping it entirely. 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 benniralamine. Will taking diphenhydramine affect my pregnancy? There is currently no research showing that diphenhydramine affects pregnancy. ◈ Does taking diphenhydramine increase the risk of miscarriage? Miscarriage can occur in any pregnancy. There is currently no research showing that diphenhydramine increases the risk of miscarriage.
◈ Does taking diphenhydramine increase the risk of birth defects?
There is a 3-5% risk of birth defects in each pregnancy. This is called the baseline risk. Based on the reviewed studies, it is unclear whether diphenhydramine increases the risk of birth defects above the baseline risk.
◈ Does taking diphenhydramine during pregnancy increase the risk of other pregnancy-related problems?
Based on the reviewed studies, it is unclear whether diphenhydramine causes other 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 taking diphenhydramine during pregnancy affect the child's future behavior or learning?
There are currently no studies exploring whether diphenhydramine causes behavioral or learning problems in children.
◈ Breastfeeding while taking diphenhydramine:
There are currently no studies on the use of diphenhydramine during breastfeeding. Diphenhydramine may cause drowsiness in adults, and high doses may have the same effect on breastfeeding infants. If you suspect your baby is lethargic (more sleepy than usual), has feeding difficulties, breathing difficulties, or weakness in their limbs, please contact your pediatrician. Therefore, this antihistamine may not be suitable for long-term use while breastfeeding. If you need to take antihistamines regularly while breastfeeding, consult your doctor to choose the most suitable medication for you. Premature infants or babies less than one month old have less developed gastrointestinal tracts than older infants. This may result in more medication entering their bloodstream. Antihistamines may reduce breast milk production, but this has not been proven. Be sure to consult your doctor about all breastfeeding-related questions.
◈ If a man takes diphenhydramine, will it affect his fertility (the ability to impregnate his partner) or increase the risk of birth defects?
Currently, there are no studies exploring whether diphenhydramine affects male fertility or increases the risk of birth defects. Generally, exposure to harmful substances by the father or sperm donor is unlikely to increase the risk of pregnancy. For more information, please refer to the "Father's Exposure to Hazardous Substances" information sheet on the MotherToBaby website at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

[1]. Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view. Curr Drug Metab. 2003 Apr;4(2):105-29.

[2]. Alpha 1-adrenergic and H1-histamine receptor control of intracellular Ca2+ in a muscle cell line: the influence of prior agonist exposure on receptor responsiveness. Mol Pharmacol. 1986 Jun;29(6):531-9.

[3]. Apoptosis of human T-cell acute lymphoblastic leukemia cells by diphenhydramine, an H1 histamine receptor antagonist. Oncol Res. 2004;14(7-8):363-72.

[4]. Spinal anesthesia with diphenhydramine and pheniramine in rats. Eur J Pharmacol. 2011 Dec 30;673(1-3):20-4.

N,N-Dimethyl-3-phenyl-3-(2-pyridyl)-1-propane is a tertiary amine compound belonging to the pyridine class. Benylamine is a first-generation alkylamine antihistamine, similar to bromobenzylamine and chlorbenzylamine. It is often used in combination with other drugs in some over-the-counter antihistamines as well as cold and flu medications. The use of benziramine as an antihistamine has been largely replaced by second-generation antihistamines (such as cetirizine and loratadine). Benylamine is a histamine H1 receptor antagonist with a weak sedative effect. It is used to treat hay fever, rhinitis, allergic dermatitis, and pruritus.
See also: Benylamine maleate (note moved to).

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Drug Indications
Benziramine is commonly used in over-the-counter medications to treat seasonal allergies or cold and flu symptoms.
FDA Label

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Mechanism of Action
Benylamine competes with histamine for histamine H1 receptors. Once bound, it acts as an inverse agonist. Reduced H1 receptor activity relieves itching and reduces vasodilation and capillary leakage, thereby reducing redness and swelling. This can be seen in the inhibition of histamine-induced wheals (swelling) and erythema (vasodilation). First-generation antihistamines such as diphenhydramine produce a sedative effect by inversely agonizing H1 receptors in the central nervous system. Diphenhydramine binds to H4 receptors, and the subsequent inverse agonist effect may also reduce itching by antagonizing inflammation.

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Pharmacodynamics
Diphenhydramine reduces edema, itching, and redness by antagonizing allergic symptoms caused by abnormal histamine release. Its antihistamine effect also produces a sedative effect by acting on the central nervous system.

C16H20N2

240.34

240.163

86-21-5

Pheniramine maleate;132-20-7

4761

Typically exists as solid at room temperature

1.018 g/cm3

84 °C20 mm Hg(lit.)

30-34 °C(lit.)

179 °F

1.556

3.165

0

2

5

18

221

0

N1C(C(CCN(C)C)C2C=CC=CC=2)=CC=CC=1

IJHNSHDBIRRJRN-UHFFFAOYSA-N

InChI=1S/C16H20N2/c1-18(2)13-11-15(14-8-4-3-5-9-14)16-10-6-7-12-17-16/h3-10,12,15H,11,13H2,1-2H3

N,N-dimethyl-3-phenyl-3-pyridin-2-ylpropan-1-amine

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.)