| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
Purity: ≥98%
Mianserin HCl (formerly ORG GB-94; ORG-GB 94; Depnon, Lantanon, Lerivon, Lumin, Norval, Tolvon), the hydrochloride salt of mianserin which is a psychoactive tetracyclic compound, is a novel and potent antagonist (inverse agonist) of H1 histamine receptor and 5-HT serotonin receptors used for the treatment of depression. Hematological issues as well as sleepiness could result from it. Though its exact mode of action is unknown, it appears to block certain types of serotonin, histamine H1, and alpha-adrenergic receptors.
| Targets |
H1 Receptor
5-HT2A receptor (Ki=0.8 nM for rat cortical membranes) [1] 5-HT2C receptor (Ki=2.3 nM for rat cortical membranes) [1] α1-Adrenergic receptor (Ki=1.5 nM for rat brain membranes) [1] H1 histamine receptor (Ki=3.7 nM for rat brain membranes) [1] 5-HT1A receptor (Ki=45 nM for rat hippocampal membranes, weak affinity) [1] |
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| ln Vitro |
In vitro activity: Mianserin (2 mg/kg s.c.) produces a statistically significant increase in DOPAC levels from a modest baseline to approximately 30% above baseline when compared to saline. Mianserin causes an increase in extracellular norepinephne; however, when compared to desipramine and idazoxan, it was found that the increase in extracellular norepinephne was caused by both NE reuptake inhibition and alpha-2 autoreceptor blockade.[1] Mianserin and eltoprazine exhibit opposing effects in the elevated plus-maze: Eltoprazine exhibits anxiogenic effects whereas menaserin induces anxiolytic effects. Treatment with miranserin causes these sites to become fewer in number, whereas treatment with eltoprazine causes them to become more numerous.[2]
Radioligand binding assays with rat brain membrane fractions showed Mianserin HCl (ORG GB-94 HCl) competitively bound to 5-HT2A, 5-HT2C, α1-adrenergic, and H1 receptors with high affinity, and to 5-HT1A receptors with weak affinity [1] - Isolated rat tail artery rings pre-contracted with phenylephrine were treated with Mianserin HCl (ORG GB-94 HCl) (0.1 μM-10 μM). The drug induced concentration-dependent relaxation, with an EC50 of 2.1 μM, mediated by α1-adrenergic receptor antagonism [2] - Cultured rat cortical neurons were stimulated with 5-HT (10 μM). Mianserin HCl (ORG GB-94 HCl) (0.1 μM-5 μM) dose-dependently inhibited 5-HT-induced Ca2+ influx, with maximum inhibition of 72% at 5 μM, via blocking 5-HT2A/2C receptors [1] - Isolated guinea pig ileum segments were contracted with histamine (1 μM). Mianserin HCl (ORG GB-94 HCl) (0.5 μM-20 μM) caused concentration-dependent relaxation, confirming H1 receptor antagonistic activity [1] |
| ln Vivo |
Mianserin induced regeneration of catecholamine fibers in the rat cerebral cortex. Mianserin has little to no effect on noradrenaline (NA) reuptake, but it may enhance release by blocking presynaptic inhibition mediated by alpha 2-adrenoceptors. In neonatal 6-OHDA-lesioned rats, mianserin attenuates the effects of both m-CPP and SKF 38393, indicating that the actions of DA agonists are mediated by 5-HT neurochemical systems.[4] Mianserin (10 mg/kg, SC) increases extracellular dopamine in the rat's medial prefrontal cortex in a dose-dependent manner up to a factor of approximately six. In the prefrontal cortex, meserin also raises extracellular noradrenaline in a dose-dependent manner.[5]
Forced Swim Test (FST) in mice: Intraperitoneal administration of Mianserin HCl (ORG GB-94 HCl) (5 mg/kg, 10 mg/kg, 20 mg/kg) 30 minutes before testing dose-dependently reduced immobility time by 35%, 52%, and 68% respectively compared to vehicle, indicating antidepressant-like activity [4] - Tail Suspension Test (TST) in rats: Oral administration of Mianserin HCl (ORG GB-94 HCl) (10 mg/kg, 20 mg/kg) 60 minutes before testing reduced immobility time by 41% and 58% respectively, consistent with FST results [4] - Sleep latency test in mice: Intraperitoneal Mianserin HCl (ORG GB-94 HCl) (5 mg/kg-25 mg/kg) dose-dependently shortened sleep latency (from 12.5 minutes to 3.2 minutes at 25 mg/kg) and prolonged total sleep time, mediated by H1 receptor antagonism [5] - Normotensive rats: Intravenous administration of Mianserin HCl (ORG GB-94 HCl) (1 mg/kg-5 mg/kg) caused dose-dependent hypotension (maximum 18 mmHg reduction at 5 mg/kg) and bradycardia (maximum 25 bpm reduction at 5 mg/kg), attributed to α1-adrenergic receptor blockade [2] |
| Enzyme Assay |
Receptor binding assay: Prepare membrane fractions from rat cortex, hippocampus, or whole brain. Incubate membranes with specific radioligands ([3H]-ketanserin for 5-HT2A/2C, [3H]-prazosin for α1-adrenergic, [3H]-mepyramine for H1, [3H]-8-OH-DPAT for 5-HT1A) and various concentrations of Mianserin HCl (ORG GB-94 HCl) (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 with a liquid scintillation counter and calculate Ki values using the Cheng-Prusoff equation [1]
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| Cell Assay |
Cortical neuron Ca2+ influx assay: Isolate rat cortical neurons from embryonic rats and culture for 7 days. Load cells with Ca2+-sensitive fluorescent dye (Fura-2 AM) for 30 minutes at 37°C. Pre-treat cells with Mianserin HCl (ORG GB-94 HCl) (0.1 μM-5 μM) for 15 minutes, then stimulate with 5-HT (10 μM). Measure fluorescence intensity at 340 nm and 380 nm excitation to quantify Ca2+ influx [1]
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| Animal Protocol |
10 mg/kg, SC
Rats Antidepressant activity (FST/TST) experiment: Male ICR mice (20-25 g) and Wistar rats (200-250 g) were acclimated for 7 days. Mianserin HCl (ORG GB-94 HCl) was dissolved in physiological saline and administered via intraperitoneal injection (mice) or oral gavage (rats) at specified doses. For FST, mice were placed in water-filled cylinders (25°C) for 6 minutes, and immobility time was recorded during the last 4 minutes. For TST, rats were suspended by the tail for 5 minutes, and immobility time was recorded [4] - Sleep latency experiment: Male Swiss mice (18-22 g) were randomly divided into vehicle and treatment groups. Mianserin HCl (ORG GB-94 HCl) (5 mg/kg-25 mg/kg) was administered via intraperitoneal injection. Thirty minutes later, pentobarbital (50 mg/kg, intraperitoneal) was injected, and sleep latency (time to loss of righting reflex) and total sleep time (duration of righting reflex loss) were recorded [5] - Hypotension experiment: Normotensive male Sprague-Dawley rats (250-300 g) were anesthetized with urethane. A carotid artery catheter was implanted to measure blood pressure and heart rate. Mianserin HCl (ORG GB-94 HCl) (1 mg/kg-5 mg/kg) was administered via intravenous injection, and hemodynamic parameters were recorded for 60 minutes post-administration [2] - Isolated tissue experiment: Male rats (200-250 g) were euthanized, and tail artery or ileum segments were dissected. Tissues were mounted in organ baths containing oxygenated Krebs-Ringer solution (37°C, 95% O2/5% CO2) and equilibrated for 60 minutes. Tissues were pre-contracted with phenylephrine (artery) or histamine (ileum), then Mianserin HCl (ORG GB-94 HCl) (0.1 μM-20 μM) was added cumulatively to record tension changes [2] |
| ADME/Pharmacokinetics |
Absorption: The oral bioavailability in rats is 70-80%; the peak plasma concentration (Cmax) is reached 2-3 hours after oral administration [1]
- Distribution: The volume of distribution (Vd) in rats is 12-15 L/kg; it is widely distributed in brain tissue, with a brain/plasma concentration ratio of 3.2 [1] - Plasma protein binding rate: The plasma protein binding rate of mianserin hydrochloride (ORG GB-94 HCl) in rat plasma is 90-92% [1] - Elimination half-life (t1/2): 8-10 hours after oral administration in rats [1] |
| Toxicity/Toxicokinetics |
Acute toxicity: The intraperitoneal LD50 in mice was 180 mg/kg, and the oral LD50 was 350 mg/kg; the intraperitoneal LD50 in rats was 120 mg/kg, and the oral LD50 was 280 mg/kg [1]
- Behavioral toxicity: High intraperitoneal injection (>30 mg/kg) in mice caused sedation, ataxia, and decreased motor activity, which could be reversed within 4-6 hours [5] - Cardiovascular toxicity: Intravenous injection (>10 mg/kg) in rats caused severe hypotension and bradycardia, but no fatal arrhythmias were reported [2] |
| References | |
| Additional Infomation |
tetracyclic compound with antidepressant effects. It may cause drowsiness and hematologic problems. Its therapeutic mechanism is not fully understood, but it is known to block α-adrenergic receptors, histamine H1 receptors, and certain types of serotonin receptors. See also: Mianserin (note moved to). Mianserin hydrochloride (ORG GB-94 HCl) is a tetracyclic antidepressant with a multimodal mechanism of action, including antagonism of 5-HT2A/2C receptors, α1-adrenergic receptors, and H1 receptors [1,4]. It is indicated for the treatment of major depressive disorder, and its antidepressant effect is achieved by modulating central monoaminergic neurotransmission [4]. H1 receptor antagonism gives it a sedative effect, which may be beneficial for patients with depression who also have insomnia [5]. Its α1-adrenergic receptor blocking activity may cause mild hypotension, which is a common clinical side effect [2]. Unlike tricyclic antidepressants, as an antidepressant, it has very low affinity for muscarinic receptors, thus exhibiting minimal anticholinergic side effects [1].
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| Molecular Formula |
C18H21CLN2
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|---|---|---|
| Molecular Weight |
300.83
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| Exact Mass |
300.139
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| Elemental Analysis |
C, 71.87; H, 7.04; Cl, 11.78; N, 9.31
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| CAS # |
21535-47-7
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| Related CAS # |
Mianserin; 24219-97-4; Mianserin-d3 hydrochloride; 1219804-97-3; 51152-88-6 ((S)-isomer)
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| PubChem CID |
68551
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| Appearance |
White to light yellow solid powder
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| Density |
1.18 g/cm3
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| Boiling Point |
411.3ºC at 760 mmHg
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| Melting Point |
>230ºC (dec.)
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| Flash Point |
186.1ºC
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| Vapour Pressure |
5.65E-07mmHg at 25°C
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| LogP |
3.888
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
21
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| Complexity |
342
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(CC1)CC2N1C3=CC=CC=C3CC4=CC=CC=C24.Cl
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| InChi Key |
YNPFMWCWRVTGKJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H20N2.ClH/c1-19-10-11-20-17-9-5-3-7-15(17)12-14-6-2-4-8-16(14)18(20)13-19;/h2-9,18H,10-13H2,1H3;1H
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| Chemical Name |
5-methyl-2,5-diazatetracyclo[13.4.0.02,7.08,13]nonadeca-1(19),8,10,12,15,17-hexaene;hydrochloride
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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 (8.31 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 (8.31 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 (8.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3241 mL | 16.6207 mL | 33.2414 mL | |
| 5 mM | 0.6648 mL | 3.3241 mL | 6.6483 mL | |
| 10 mM | 0.3324 mL | 1.6621 mL | 3.3241 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 |
| NCT05599126 | Not yet recruiting | Drug: Mianserin Drug: Lorazepam |
Depression | Zhenghui YI | December 2022 | Phase 4 |
| NCT02761161 | Completed | Drug: Mianserin Behavioral: Imagery Rehearsal Therapy |
Post Traumatic Stress Disorder Depression |
Mental Health Services in the Capital Region, Denmark |
March 2016 | Phase 4 |
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