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Maprotiline HCl

Alias:
Cat No.:V1116 Purity: ≥98%
Maprotiline HCl (Psymion; Ludiomil), the hydrochloride salt of Maprotiline which is a tetracyclic antidepressant, is a selective noradrenalin reuptake inhibitor that has been approved for the treatment of depression.
Maprotiline HCl
Maprotiline HCl Chemical Structure CAS No.: 10347-81-6
Product category: Adrenergic Receptor
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
500mg
1g
2g
5g
Other Sizes

Other Forms of Maprotiline HCl:

  • Maprotiline-d5 hydrochloride (Maprotiline d5 hydrochloride)
  • Maprotiline-d3 HCl
  • Maprotiline
Official Supplier of:
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Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Maprotiline HCl (Psymion; Ludiomil), the hydrochloride salt of Maprotiline which is a tetracyclic antidepressant, is a selective noradrenalin reuptake inhibitor that has been approved for the treatment of depression.

Biological Activity I Assay Protocols (From Reference)
Targets
Adrenergic Receptor
ln Vitro

In vitro activity: Maprotiline has an IC50 of 5.2 μM for HERG channels expressed in HEK cells and a 24 μM IC50 for HERG channels expressed in oocytes. While it has no discernible effect on closed channels, maprotiline blocks open channels.[1] Maprotiline is an atetracyclic antidepressant that notably lacks its ability to inhibit serotonergic uptake but effectively inhibits noradrenaline uptake. In comparison to amitriptyline, maprotiline exhibits a notably less pronounced alpha-adrenergic blocking activity.[2] In Neuro-2a cells, maprotiline reduces cell viability in a concentration- and time-dependent manner. Maprotiline raises caspase-3 activation and causes apoptosis. Additionally, maprotiline causes an increase in [Ca(2+)](i), which is caused by the intracellular Ca(2+) that is stored in the endoplasmic reticulum being mobilized.[3]

ln Vivo
Systemic, intracerebroventricular and subplantar application of maprotiline significantly inhibited peripheral edema, but intrathecal maprotiline did not alter the degree of paw swelling. The applied antagonists failed to change the anti-inflammatory activity of maprotiline. Conclusion: These results demonstrate that maprotiline has a potent anti-inflammatory effect and this effect is linked to the peripheral and supraspinal actions of the drug.[5]
The effects of acute and chronic administration of maprotiline (5, 10 or 20 mg/kg, intraperitoneally) were assessed on inhibitory avoidance in male mice. Acute administration of maprotiline before training did not effect training phase latencies, but impaired performance (i.e. produced shorter latencies) in the test at doses of 5 and 20 mg/kg. When given after training, the drug did not modify test latencies at any of the doses used. Chronic administration for 21 days (interrupted 24 h before training) also shortened latencies in the test but not in training. An experiment on the acute effects of maprotiline on analgesia (determination of flinch and jump thresholds for increasing electric foot shock levels), at the doses stated, was carried out on naive animals. No analgesic effect of the drug was found. Taken together, the results indicate that acute maprotiline produces anterograde amnesia, and tolerance does not appear after 21 days of treatment.[6]
Maprotiline causes a significant increase in the expression of the GluR1 and GluR2/3 subunits in the mouse nucleus accumbens and dorsal striatum, as shown by immunohistochemistry; additionally, a significant increase in the expression of GluR1 and GluR2/3 in the hippocampus, as shown by Western blot analysis.[4] Due to the drug's peripheral and supraspinal actions, maprotiline has a strong anti-inflammatory effect on rats. [5] When given prior to training, maprotiline hinders learning; however, when given after training, no statistically significant effect is seen.[6]
Enzyme Assay
Antidepressants are generally used for treatment of various mood and anxiety disorders. Several studies have shown the anti-tumor and cytotoxic activities of some antidepressants, but the underlying mechanisms were unclear. Maprotiline is a tetracyclic antidepressant and possesses a highly selective norepinephrine reuptake ability. We found that maprotiline decreased cell viability in a concentration- and time-dependent manner in Neuro-2a cells. Maprotiline induced apoptosis and increased caspase-3 activation. The activation of caspase-3 by maprotiline appears to depend on the activation of JNK and the inactivation of ERK. Maprotiline also induced [Ca(2+)](i) increases which involved the mobilization of intracellular Ca(2+) stored in the endoplasmic reticulum. Pretreatment with BAPTA/AM, a Ca(2+) chelator, suppressed maprotiline-induced ERK phosphorylation, enhanced caspase-3 activation and increased maprotiline-induced apoptosis. In conclusion, maprotiline induced apoptosis in Neuro-2a cells through activation of JNK-associated caspase-3 pathways. Maprotiline also evoked an anti-apoptotic response that was both Ca(2+)- and ERK-dependent.[1]
Cell Assay
Many drugs block delayed rectifier K+ channels and prolong the cardiac action potential duration. Here we investigate the molecular mechanisms of voltage-dependent block of human ether-a-go-go-related gene (HERG) K+ channels expressed in cells HEK-293 and Xenopus oocytes by maprotiline. The IC50 determined at 0 mV on HERG expressed HEK-293 cell and oocytes was 5.2 and 23.7 microM, respectively. Block of HERG expressed in oocytes by maprotiline was enhanced by progressive membrane depolarization and accompanied by a negative shift in the voltage dependence of channel activation. The potency of maprotiline was reduced 7-fold by point mutation of a key aromatic residue (F656T) and 3-fold for Y652A, both located in the S6 domain. The mutation Y652A inverted the voltage dependence of HERG channel block by maprotiline. Together, these results suggest that voltage-dependent block of HERG results from gating dependent changes in the accessibility of Y652, a critical component of the drug binding site.[1]
Animal Protocol
Firstly, the anti-inflammatory effect of systemic maprotiline (12.5, 25 and 50 mg kg(-1)) was assessed using a paw edema model. Secondly, different doses of maprotiline were administrated intracerebroventricularly, intrathecally and locally before carrageenan challenge. Finally, we tried to reverse the anti-inflammatory effect of maprotiline by propranolol (10 mg kg(-1)), prazosin (4 mg kg(-1)), yohimbine (10 mg kg(-1)), naloxone (4 mg kg(-1)) and mifepristone (5 mg kg(-1)).[5]
State-dependent learning (SDL) is a phenomenon in which the retrieval of newly acquired information is possible if the subject is in the same physiological state as during the encoding phase. SDL makes it possible to separate the effects of drugs per se on learning from the effects due to changes in drug state during the task. The present work was designed to investigate whether the antidepressants amitriptyline (30 mg/kg), maprotiline (25 mg/kg), and fluoxetine (15 mg/kg) produce SDL of the inhibitory avoidance conditioning in male and female CD1 mice. In three separate experiments, independent groups were used for each pharmacological treatment and for each sex using a 2 x 2 experimental design. The results do not show SDL in any of the drugs. In the case of amitriptilyline, the data can be attributed to a memorization deficit, while the maprotiline results are interpreted as simultaneously influenced by memorization deficit and performance facilitation due to motor impairment. Fluoxetine treatment did not produce any deteriorating effect on the conditioning. Drugs had some different effects on the performance of males and females, males showing a slightly higher deterioration than females with administration of amitriptyline and maprotiline. This study shows that these antidepressants affect the acquisition/consolidation but not the retrieval process in the inhibitory avoidance learning.[2]
ADME/Pharmacokinetics
Absorption, Distribution and Excretion
Slowly, but completely absorbed from the GI tract following oral administration.
Approximately 60% of a single orally administered dose is excreted in urine as conjugated metabolites within 21 days; 30% is eliminated in feces.
Maprotiline and its metabolites may be detected in the lungs, liver, brain, and kidneys; lower concentrations may be found in the adrenal glands, heart and muscle. Maprotiline is readily distributed into breast milk to similar concentrations as those in maternal blood.
Metabolism / Metabolites
Hepatic. Maprotiline is metabolized by N-demethylation, deamination, aliphatic and aromatic hydroxylations and by formation of aromatic methoxy derivatives. It is slowly metabolized primarily to desmethylmaprotiline, a pharmacologically active metabolite. Desmethylmaprotiline may undergo further metabolism to maprotiline-N-oxide.
Maprotiline has known human metabolites that include 2-hydroxy-maprotiline, desmethylmaprotiline, and 3-hydroxy-maprotiline.
Hepatic. Maprotiline is metabolized by N-demethylation, deamination, aliphatic and aromatic hydroxylations and by formation of aromatic methoxy derivatives. It is slowly metabolized primarily to desmethylmaprotiline, a pharmacologically active metabolite. Desmethylmaprotiline may undergo further metabolism to maprotiline-N-oxide.
Route of Elimination: Approximately 60% of a single orally administered dose is excreted in urine as conjugated metabolites within 21 days; 30% is eliminated in feces.
Half Life: Average ~ 51 hours (range: 27-58 hours)
Biological Half-Life
Average ~ 51 hours (range: 27-58 hours)
Toxicity/Toxicokinetics
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because there is little published experience with maprotiline during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Although it is structurally a tetracyclic compound, maprotiline has pharmacologic actions similar to the tricyclic antidepressants.
Follow-up for 1 to 3 years in a group of 20 breastfed infants whose mothers were taking a tricyclic antidepressant found no adverse effects on growth and development. Two small controlled studies indicate that other tricyclic antidepressants have no adverse effect on infant development.
In another study, 25 infants whose mothers took a tricyclic antidepressant during pregnancy and lactation were assessed formally between 15 to 71 months and found to have normal growth and development. One of the mothers was taking maprotiline.
◉ Effects on Lactation and Breastmilk
Maprotiline has caused increased serum prolactin levels and galactorrhea in nonpregnant, nonnursing patients. The clinical relevance of these findings in nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
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 maprotiline.
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.
Protein Binding
88%
References

[1]. Eur J Pharmacol . 2006 Feb 15;531(1-3):1-8.

[2]. Behav Brain Res . 2006 Jan 6;166(1):150-8.

[3]. Toxicology . 2013 Feb 8:304:1-12.

[4]. Cancer Lett . 2009 Apr 8;276(1):14-20.

[5]. Inflamm Res . 2010 Dec;59(12):1053-9.

[6]. Behav Brain Res . 2000 Apr;109(1):1-7.

Additional Infomation
Maprotiline is a member of anthracenes.
Maprotiline is a tetracyclic antidepressant with similar pharmacological properties to tricyclic antidepressants (TCAs). Similar to TCAs, maprotiline inhibits neuronal norepinephrine reuptake, possesses some anticholinergic activity, and does not affect monoamine oxidase activity. It differs from TCAs in that it does not appear to block serotonin reuptake. Maprotiline may be used to treat depressive affective disorders, including dysthymic disorder (depressive neurosis) and major depressive disorder. Maprotiline is effective at reducing symptoms of anxiety associated with depression.
Maprotiline is a tetracyclic antidepressant with similar pharmacological properties to tricyclic antidepressants (TCAs). Similar to TCAs, maprotiline inhibits neuronal norepinephrine reuptake, possesses some anticholinergic activity, and does not affect monoamine oxidase activity. It differs from TCAs in that it does not appear to block serotonin reuptake. Maprotiline may be used to treat depressive affective disorders, including dysthymic disorder (depressive neurosis) and major depressive disorder. Maprotiline is effective at reducing symptoms of anxiety associated with depression.
A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use.
Drug Indication
For treatment of depression, including the depressed phase of bipolar depression, psychotic depression, and involutional melancholia, and may also be helpful in treating certain patients suffering severe depressive neurosis.
Mechanism of Action
Maprotiline exerts its antidepressant action by inhibition of presynaptic uptake of catecholamines, thereby increasing their concentration at the synaptic clefts of the brain. In single doses, the effect of maprotiline on the EEG revealed a rise in the alpha-wave density, a reduction of the alpha-wave frequency and an increase in the alpha-wave amplitude. However, as with other tricyclic antidepressants, maprotiline lowers the convulsive threshold. Maprotiline acts as an antagonist at central presynaptic α2-adrenergic inhibitory autoreceptors and hetero-receptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity. Maprotiline is also a moderate peripheral α1 adrenergic antagonist, which may explain the occasional orthostatic hypotension reported in association with its use. Maprotiline also inhibits the amine transporter, delaying the reuptake of noradrenaline and norepinephrine. Lastly, maprotiline is a strong inhibitor of the histamine H1 receptor, which explains its sedative actions.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C20H24CLN
Molecular Weight
313.86
Exact Mass
313.159
Elemental Analysis
C, 76.53; H, 7.71; Cl, 11.30; N, 4.46
CAS #
10347-81-6
Related CAS #
Maprotiline-d5 hydrochloride; 1794942-12-3; Maprotiline-d3 hydrochloride; 1329496-63-0; Maprotiline; 10262-69-8; 58902-67-3 (mesylate)
PubChem CID
4011
Appearance
White to off-white solid powder
Boiling Point
399.6ºC at 760 mmHg
Melting Point
230-232ºC
Flash Point
187.7ºC
Vapour Pressure
9.8E-08mmHg at 25°C
LogP
5.404
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
1
Rotatable Bond Count
4
Heavy Atom Count
21
Complexity
339
Defined Atom Stereocenter Count
0
SMILES
Cl[H].N([H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C12C3=C([H])C([H])=C([H])C([H])=C3C([H])(C3=C([H])C([H])=C([H])C([H])=C13)C([H])([H])C2([H])[H]
InChi Key
NZDMFGKECODQRY-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H23N.ClH/c1-21-14-6-12-20-13-11-15(16-7-2-4-9-18(16)20)17-8-3-5-10-19(17)20;/h2-5,7-10,15,21H,6,11-14H2,1H3;1H
Chemical Name
N-methyl-3-(1-tetracyclo[6.6.2.02,7.09,14]hexadeca-2,4,6,9,11,13-hexaenyl)propan-1-amine;hydrochloride
Synonyms

Psymion; Ludiomil; Maprotilline HCl; Ciba 34276 Ba; 9-(gamma-Methylaminopropyl)-9,10-dihydro-9,10-ethanoanthracene hydrochloride; Maprotiline Hydrochlorine; Maprotiline Hydrochlorine; Maprotiline Hcl

HS Tariff Code
2934.99.9001
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.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 63~83.3 mg/mL (200.7~265.5 mM)
Water: <1 mg/mL
Ethanol: ~24 mg/mL (~76.5 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.63 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 20.8 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: ≥ 2.08 mg/mL (6.63 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 20.8 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: ≥ 2.08 mg/mL (6.63 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


Solubility in Formulation 4: 2 mg/mL (6.37 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.1861 mL 15.9307 mL 31.8613 mL
5 mM 0.6372 mL 3.1861 mL 6.3723 mL
10 mM 0.3186 mL 1.5931 mL 3.1861 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.

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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.
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Clinical Trial Information
Pharmacovigilance in children and adolescents:
EudraCT: 2013-004881-33
Phase: Phase 3
Status: Completed
Date: 2017-02-28
Pharmacovigilance in Gerontopsychiatric Patients
CTID: NCT02374567
Phase: Phase 3
Status: Terminated
Date: 2018-02-28
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