Absorption, Distribution and Excretion
Absorbed following oral administration.
A pharmacokinetic study with mianserin HCl was performed in six healthy male subjects. The subjects were treated on different occasions intravenously with a constant-rate infusion of 5 mg mianserin HCl in 1 hr, orally with a single dose of 60 mg as two tablets of 30 mg each and with 60 mg as an oral solution. The wash-out period between treatments was 1 month. Blood samples were taken at predetermined times over a period of 120 hr following dosing. The mianserin concentration in the plasma samples was determined and the results were pharmacokinetically analyzed. The intravenous data could be adequately described by a 3-compartment model and the oral data by a 2-compartment model, both with first-order transfer and elimination rate constants. The mean plasma clearance of mianserin was found to be 19 +/- 2 L/hr (mean +/- SEM), the kinetic volume of distribution 444 +/- 250 L, the steady-state volume of distribution 242 +/- 171 L and the elimination half-life 33 +/- 5 hr. The absolute bioavailability in terms of extent of absorption was 22 +/- 3% for the solution and 20 +/- 3% for the tablets. The mean peak level for the solution was 79 +/- 11 ng/mL and for the tablets 54 +/- 5 ng /mL; mean peak time for the solution was 1.1 +/- 0.2 hr and for the tablets 1.4 +/- 0.2 hr. The mean absorption half-life for the solution was 0.43 +/- 0.13 hr and for the tablets 0.39 +/- 0.11 hr.
We studied mianserin kinetics after a single (60 mg) dose in eight inpatients suffering from depression. There was a considerable interpatient variability in plasma levels. Mean peak plasma levels (+/- SEM) were 114 +/- 26 ng/ml and were reached between 1 and 3 hr. The decline of mianserin levels in plasma was biphasic. The mean elimination t 1/2 was 21.6 +/- 3.1 hr and ranged from 10.7 to 40.8 hr. The estimated first-pass loss ranged from 26% to 48% (mean, 37%) and was lower than that reported for tertiary amine tricyclic antidepressants. The mean apparent volume of distribution (15.7 +/- 2.2 L/kg; 9.7 to 28.8 L/kg) was in the range of that for imipramine but somewhat lower than for maprotiline. Apparent total body clearance ranged from 0.33 to 0.81 L/hr/kg (mean +/- SEM, 0.52 +/- 0.05 L/hr/kg) and was of the order of that after maprotiline. Our results indicate that mianserin kinetics are in most respects similar to those of tertiary amine tricyclic antidepressants (e.g., imipramine) and the tetracyclic maprotiline.

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Metabolism / Metabolites
Hepatic.
Mianserin metabolism was studied in female humans, rabbits, and rats. ... In human females, unchanged mianserin, 8-hydroxymianserin and mianserin-2-oxide were isolated and identified in urine. The two metabolites were over 60 percent of the total urinary radioactivity; conjugated and unconjugated mianserin accounted for approximately 35 percent. In rabbits, mianserin was metabolized largely as 8-hydroxymianserin and an unidentified ester of 8-hydroxymianserin; only about 2.4 percent was unchanged mianserin. Small amounts of 2-formyldesmethylmianserin were isolated. The principal metabolite in rats was 8-hydroxydesmethylmianserin. Rats metabolized mianserin principally to 8-hydroxy compounds and to a lesser extent to demethylated metabolites. The authors conclude that mianserin is metabolized by three main pathways: 8-hydroxylation, demethylation, and 2-oxide formation. /Mianserin HCl/
To measure steady-state plasma concentrations of mianserin and its major active metabolite, desmethylmianserin, and to analyze the effects of various clinical factors on these plasma concentrations, steady-state plasma concentrations of mianserin and desmethylmianserin were measured in 76 depressed patients, ages 20-70 yr, receiving 30 mg/day mianserin at bedtime for 3 wk with doses increased up to 60 mg/day if needed. There were considerable interindividual variations in the steady-state plasma concentrations of these compounds; the plasma concentrations of mianserin plus desmethylmianserin were within the therapeutic range in only 43% of the patients. With advancing age, the plasma concentrations of mianserin increased significantly, while those of mianserin plus desmethylmianserin remained unchanged. Sex, smoking, and coadministration of benzodiazepines did not affect the drug's metabolism. There was no evidence that the kinetics of these compounds were nonlinear with increasing doses.
Mianserine has known human metabolites that include 8-Hydroxymianserin, Desmethylmianserin, and Mianserin N-oxide.

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Biological Half-Life
10-17 hours
The pharmacokinetics of mianserin hydrochloride have been determined in eight normal healthy volunteers, mean age 27, and 14 elderly patients, mean age 76. Mianserin was administered to volunteers by intravenous infusion (0.011 mg/kg/min for 15 min) and, on another occasion, by mouth, in a single dose of 30 mg. Elderly patients received a single oral dose of 40-60 mg. The terminal elimination half-life was significantly prolonged in the elderly. In young subjects it was 9.6 +/- 1.9 (s.d.) hr. In the elderly it was 27 +/- 13.1 (s.d.) hr. Apparent oral clearance was significantly reduced in the elderly. In young subjects it was 87.1 +/- 32 (s.d.) hr. In the elderly, it was 38.1 +/- 14.8 (s.d.) hr. These kinetic differences may have an important bearing on the sedative effects of mianserin.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Mianserin is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. Limited information indicates that maternal doses up to 60 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Until more data are available, mianserin should be used with careful monitoring during breastfeeding.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge. The antidepressants used by the mothers were not specified.
A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis. None of the mothers were taking mianserin.
In a study of 80,882 Norwegian mother-infant pairs from 1999 to 2008, new postpartum antidepressant use was reported by 392 women and 201 reported that they continued antidepressants from pregnancy. Compared with the unexposed comparison group, late pregnancy antidepressant use was associated with a 7% reduced likelihood of breastfeeding initiation, but with no effect on breastfeeding duration or exclusivity. Compared with the unexposed comparison group, new or restarted antidepressant use was associated with a 63% reduced likelihood of predominant, and a 51% reduced likelihood of any breastfeeding at 6 months, as well as a 2.6-fold increased risk of abrupt breastfeeding discontinuation. Specific antidepressants were not mentioned.

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Protein Binding
90%

[1]. The atypical antidepressant mianserin exhibits agonist activity at κ-opioid receptors. Br J Pharmacol. 2012 Nov;167(6):1329-41.

[2]. Roeder T. High-affinity antagonists of the locust neuronal octopamine receptor. Eur J Pharmacol. 1990 Nov 27;191(2):221-4.

Mianserin is a dibenzoazepine (specifically 1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine) methyl-substituted on N-2. Closely related to (and now mostly superseded by) the tetracyclic antidepressant mirtazapinean, it is an atypical antidepressant used in the treatment of depression throughout Europe and elsewhere. It has a role as an antidepressant, a histamine agonist, a sedative, an alpha-adrenergic antagonist, an adrenergic uptake inhibitor, a serotonergic antagonist, a H1-receptor antagonist, an EC 3.4.21.26 (prolyl oligopeptidase) inhibitor and a geroprotector.
A tetracyclic compound with antidepressant effects. Mianserin was previously available internationally, however in most markets it has been phased out in favour of [mirtazapine].
A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors.

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Drug Indication
For the treatment of depression.

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Mechanism of Action
Mianserin's mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors.

C18H20N2

264.3648

264.163

24219-97-4

Mianserin hydrochloride;21535-47-7

4184

Typically exists as solid at room temperature

1.18g/cm3

411.3ºC at 760mmHg

186.1ºC

3.086

0

2

0

20

342

0

CN(CC1)CC2N1C3=CC=CC=C3CC4=CC=CC=C24

UEQUQVLFIPOEMF-UHFFFAOYSA-N

InChI=1S/C18H20N2/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

5-methyl-2,5-diazatetracyclo[13.4.0.02,7.08,13]nonadeca-1(19),8,10,12,15,17-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)

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.)