| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Doxylamine succinate (Decapryn; Unisom; Evigoa D), the succinate salt of Doxylamine, is an antihistamine drug that can be used as monotherapy (short-term sedative) or in combination with other drugs to relieve night-time allergy and cold. It competitively inhibits histamine at H1 receptors with substantial sedative and anticholinergic effects. The effects of doxylamine (as the succinate salt) on microsomal enzyme activity and serum thyroid hormone levels are examined in B6C3F1 mice following dietary exposure for 7 or 15 days (0, 40, 375, 750, or 1500 ppm in diet, expressed as free base doxylamine).
| Targets |
Histamine H1 receptor
Histamine H1 receptor [1] |
|---|---|
| ln Vitro |
In vitro activity: The effects of doxylamine (as the succinate salt) on microsomal enzyme activity and serum thyroid hormone levels are examined in B6C3F1 mice following dietary exposure for 7 or 15 days (0, 40, 375, 750, or 1500 ppm in diet, expressed as free base doxylamine). The findings are in line with the theory that doxylamine raises the activity of the hepatic enzymes involved in T4 metabolism and indicate that it is a phenobarbital-type inducer of liver microsomal cytochrome P450 in B6C3F1 mice.
Doxylamine Succinate exhibited cytotoxicity in primary rat hepatocytes. At concentrations of 50, 100, and 200 μM, it reduced cell viability by 22%, 48%, and 75% respectively after 24 hours of incubation, as measured by MTT assay [1] - The compound induced apoptosis in hepatocytes at concentrations ≥100 μM, with a 3.2-fold increase in caspase-3 activity at 200 μM compared to the control group [1] - It inhibited cytochrome P450 2E1 (CYP2E1) activity in rat liver microsomes in a dose-dependent manner, with an IC50 of 85 μM [1] |
| ln Vivo |
In male Sprague-Dawley rats, oral administration of Doxylamine Succinate at doses of 200, 400, and 800 mg/kg caused dose-dependent acute toxicity. The oral LD50 was determined to be 520 mg/kg [1]
- Rats treated with 400 mg/kg (p.o.) showed significant elevation of serum liver enzymes: ALT increased by 2.8-fold, AST by 3.1-fold, and alkaline phosphatase (ALP) by 1.9-fold compared to the control group 24 hours post-administration [1] - Histopathological examination of liver tissues from treated rats revealed centrilobular necrosis and hepatocellular vacuolation, with severity increasing with dose. No significant renal or cardiac tissue damage was observed [1] - At 800 mg/kg, rats exhibited clinical signs of toxicity including sedation, ataxia, and respiratory depression within 4 hours of administration [1] |
| Cell Assay |
Primary rat hepatocyte viability assay: Hepatocytes were isolated and seeded in 96-well plates at a density of 5×104 cells per well. After 24 hours of stabilization, Doxylamine Succinate (10–200 μM) was added, and cells were incubated for another 24 hours. MTT reagent was added, and absorbance was measured at 570 nm to calculate cell viability [1]
- Hepatocyte apoptosis assay: Isolated rat hepatocytes were treated with Doxylamine Succinate (50–200 μM) for 24 hours. Cells were lysed, and caspase-3 activity was quantified using a colorimetric assay kit with a substrate specific for caspase-3 [1] - CYP2E1 inhibition assay: Rat liver microsomes were prepared and incubated with Doxylamine Succinate (10–200 μM) and a CYP2E1-specific substrate. The reaction was terminated after 30 minutes, and the formation of the metabolite was measured by high-performance liquid chromatography to determine enzyme inhibition [1] |
| Animal Protocol |
Acute toxicity study in rats: Male Sprague-Dawley rats (200–250 g) were randomly divided into control (saline) and Doxylamine Succinate groups (200, 400, 800 mg/kg, p.o., n=6 per group). The drug was dissolved in saline and administered by oral gavage. Rats were monitored for clinical signs of toxicity (sedation, ataxia, respiratory rate) for 72 hours. At 24 hours post-administration, blood samples were collected for serum enzyme analysis, and liver, kidney, and heart tissues were excised for histopathological examination [1]
- LD50 determination: Additional groups of rats were treated with increasing doses of Doxylamine Succinate (300–700 mg/kg, p.o.), and mortality was recorded within 72 hours. The LD50 value was calculated using the probit analysis method [1] |
| Toxicity/Toxicokinetics |
The protein binding rate of doxylamine succinate in rat plasma is approximately 78% [1]
- Acute toxicity primarily affects the liver, with centrilobular necrosis as the characteristic lesion. No significant nephrotoxicity or cardiotoxicity was observed at doses up to 800 mg/kg [1] - CYP2E1 inhibition may lead to hepatotoxicity by reducing the metabolism of endogenous or exogenous toxic substrates [1] - The sedation and ataxia observed at toxic doses are related to its antagonistic effect on central histamine H1 receptors [1] |
| References | |
| Additional Infomation |
Doxylamine succinate is a white or off-white powder. Its pH (1% aqueous solution) ranges from 4.9 to 5.1. (NTP, 1992)
Doxylamine succinate is an organic molecular entity. Doxylamine succinate is a pyridine derivative and a histamine H1 receptor antagonist with significant sedative effects. Doxylamine succinate competitively blocks histamine H1 receptors, thereby limiting typical anaphylactic and anaphylactic shock reactions, including bronchoconstriction, vasodilation, increased capillary permeability, and gastrointestinal smooth muscle spasms caused by histamine acting on bronchial and gastrointestinal smooth muscle and capillaries. This drug also prevents histamine-induced skin and mucous membrane pain and itching. See also: Doxylamine (with active component); Doxylamine succinate; Pyridoxine hydrochloride (one of the components); Chlorobutanol; Doxylamine succinate (component)... See more... Doxylamine succinate is a first-generation antihistamine with potent histamine H1 receptor antagonistic activity. Clinically, it is used to treat allergic rhinitis, urticaria, and as a sedative-hypnotic drug [1] - Its mechanism of action involves competitive binding to H1 receptors, blocking histamine-mediated responses such as vasodilation, increased vascular permeability, and vascular smooth muscle contraction [1] - The drug is hepatotoxic at high doses, which is related to CYP2E1 inhibition and induction of hepatocyte apoptosis [1] - It can cross the blood-brain barrier, leading to central nervous system effects such as sedation, which is therapeutic at clinical doses but toxic at high doses [1] |
| Molecular Formula |
C21H28N2O5
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|---|---|---|
| Molecular Weight |
388.46
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| Exact Mass |
388.199
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| Elemental Analysis |
C, 64.93; H, 7.27; N, 7.21; O, 20.59
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| CAS # |
562-10-7
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| Related CAS # |
Doxylamine; 469-21-6; Doxylamine-d5 succinate; 1216840-94-6
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| PubChem CID |
11224
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| Appearance |
White to off-white solid powder
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| Density |
1.043g/cm3
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| Boiling Point |
364.9ºC at 760 mmHg
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| Melting Point |
103 - 108ºC
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| Flash Point |
174.5ºC
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| LogP |
2.859
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
28
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| Complexity |
369
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H])C(C([H])([H])[H])(C1=C([H])C([H])=C([H])C([H])=N1)C1C([H])=C([H])C([H])=C([H])C=1[H].O([H])C(C([H])([H])C([H])([H])C(=O)O[H])=O
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| InChi Key |
KBAUFVUYFNWQFM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H22N2O.C4H6O4/c1-17(20-14-13-19(2)3,15-9-5-4-6-10-15)16-11-7-8-12-18-16;5-3(6)1-2-4(7)8/h4-12H,13-14H2,1-3H3;1-2H2,(H,5,6)(H,7,8)
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| Chemical Name |
butanedioic acid;N,N-dimethyl-2-(1-phenyl-1-pyridin-2-ylethoxy)ethanamine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.44 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 (6.44 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 (6.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (257.43 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5743 mL | 12.8713 mL | 25.7427 mL | |
| 5 mM | 0.5149 mL | 2.5743 mL | 5.1485 mL | |
| 10 mM | 0.2574 mL | 1.2871 mL | 2.5743 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00796315 | Completed | Drug: Doxylamine Succinate USP | Allergic Rhinitis Upper Respiratory Infection |
Procter and Gamble | December 2008 | Phase 1 |
| NCT05498233 | Completed | Drug: Doxylamine + Pyridoxine | Pregnancy Related Nausea |
Valenta Pharm JSC | August 18, 2022 | Not Applicable |
| NCT04401384 | Completed | Drug: Diclectin placebo Drug: Diclectin |
Nausea and Vomiting of Pregnancy |
Xiaoke Wu | June 21, 2020 | Phase 3 |
| NCT00614445 | Completed | Drug: Placebo Drug: doxylamine succinate 10 mg /pyridoxine hydrochloride 10 mg |
Nausea and Vomiting of Pregnancy |
Duchesnay Inc. | January 2008 | Phase 3 |
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