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| Targets |
(Z)-10-Hydroxy Nortriptyline targets the norepinephrine transporter (NET), similar to its parent drug Nortriptyline. By inhibiting NET, it blocks the reuptake of norepinephrine from the synaptic cleft, increasing norepinephrine availability in the synapse. The compound also likely targets the serotonin transporter (SERT) to some extent, characteristic of tricyclic antidepressants. It has lower anticholinergic effects compared to Nortriptyline, suggesting reduced activity at muscarinic acetylcholine receptors. The compound contributes to the antidepressant effects of Nortriptyline.
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| ln Vitro |
In vitro studies have demonstrated that (Z)-10-Hydroxy Nortriptyline shows potent norepinephrine transporter (NET) inhibitory activity. It has lower anticholinergic effects compared to its parent drug Nortriptyline. As a metabolite of Nortriptyline, it contributes to the overall pharmacological profile of the parent drug. The compound is used as a research tool for studying antidepressant pharmacology and metabolism. Its activity at other targets such as serotonin transporters and histamine receptors is characteristic of tricyclic antidepressants.
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| ln Vivo |
In vivo studies have shown that (Z)-10-Hydroxy Nortriptyline, as a metabolite of Nortriptyline, contributes to the antidepressant effects of the parent drug. Nortriptyline is used to relieve the symptoms of depression. The metabolite's potent NET inhibitory activity translates to in vivo effects on norepinephrine neurotransmission. Its lower anticholinergic effects compared to Nortriptyline suggest a more favorable side effect profile. The compound is used in pharmacokinetic and pharmacodynamic studies of tricyclic antidepressants.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for (Z)-10-Hydroxy Nortriptyline typically involve neurotransmitter transporter binding studies. The norepinephrine transporter (NET) is incubated with increasing concentrations of the compound (0.1 nM - 10 μM) and a fixed concentration of a radiolabeled NET ligand (e.g., ³H-nisoxetine) in binding buffer at room temperature for 1-2 hours. Bound and free radioligand are separated by rapid filtration through glass fiber filters. Radioactivity is measured by liquid scintillation counting. IC50 values are calculated from dose-response curves by nonlinear regression, and Ki values are derived using the Cheng-Prusoff equation. Similar assays can be performed for serotonin transporter (SERT) and dopamine transporter (DAT). Muscarinic receptor binding can be assessed using ³H-QNB.
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| Cell Assay |
For in vitro cell-based assays, neuronal cell lines or cells expressing recombinant NET are cultured in appropriate media. Cells are treated with (Z)-10-Hydroxy Nortriptyline at concentrations ranging from 0.1 nM - 10 μM for 1-24 hours. Norepinephrine uptake is measured by incubating cells with ³H-norepinephrine with or without compound pretreatment, followed by scintillation counting of cell-associated radioactivity. IC50 values for uptake inhibition are calculated. Cell viability is assessed by MTT or CCK-8 assays. The compound's lower anticholinergic effects compared to Nortriptyline can be confirmed in muscarinic receptor functional assays.
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| Animal Protocol |
In vivo animal studies with (Z)-10-Hydroxy Nortriptyline are typically conducted in the context of studying the pharmacology of Nortriptyline and its metabolites. Rodent models of depression (e.g., forced swim test, tail suspension test) are used to assess antidepressant-like effects. The compound is administered orally or intraperitoneally at doses determined from pharmacokinetic studies. Norepinephrine and serotonin levels in brain regions are measured by microdialysis or HPLC. Behavioral observations are conducted at specific time points following drug administration. The compound's contribution to the antidepressant effects of Nortriptyline can be assessed by comparing the effects of Nortriptyline with and without metabolite formation.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
E-10-hydroxynortriptyline is a known human metabolite of nortriptyline. (Z)-10-Hydroxy Nortriptyline has a molecular weight of 279.38 g/mol and molecular formula C19H21NO. The compound is a metabolite of Nortriptyline, formed by CYP450-mediated hydroxylation. Pharmacokinetic properties are similar to other tricyclic antidepressant metabolites, with moderate protein binding and hepatic metabolism. The compound is primarily excreted via urine as conjugates. It is used as a research tool for studying antidepressant pharmacology and metabolism. The compound is not intended for therapeutic use. |
| Toxicity/Toxicokinetics |
As a metabolite of Nortriptyline, (Z)-10-Hydroxy Nortriptyline is expected to have a similar toxicity profile to other tricyclic antidepressant metabolites. Tricyclic antidepressants can cause side effects including dry mouth, sedation, dizziness, and cardiac effects at high doses. The compound's lower anticholinergic effects compared to Nortriptyline suggest a reduced risk of anticholinergic side effects. The compound is used in very small quantities as a research reagent and does not pose significant toxicity risks under normal handling.
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| References | |
| Additional Infomation |
(Z)-10-Hydroxy Nortriptyline ((Z)-10-Hydroxynortriptyline) is a metabolite of Nortriptyline, a tricyclic antidepressant and the main active metabolite of Amitriptyline. It has a molecular weight of 279.38 g/mol and molecular formula C19H21NO. The compound shows potent norepinephrine transporter (NET) inhibitory activity and has lower anticholinergic effects compared to its parent drug Nortriptyline. It contributes to the antidepressant effects of Nortriptyline. (Z)-10-Hydroxy Nortriptyline is not FDA-approved and is intended for research and analytical use only.
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| Molecular Formula |
C₁₉H₂₁NO
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|---|---|
| Molecular Weight |
279.38
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| Exact Mass |
279.162
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| CAS # |
47132-19-4
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| Related CAS # |
(Z)-10-Hydroxynortriptyline-d3;(E)-10-Hydroxynortriptyline;47132-16-1;(E)-10-Hydroxynortriptyline maleate;74853-74-0
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| PubChem CID |
6420504
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| Appearance |
White to off-white solid powder
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| LogP |
3.708
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
21
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| Complexity |
365
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CNCC/C=C\1/C2=CC=CC=C2CC(C3=CC=CC=C31)O
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| InChi Key |
VAGXZGJKNUNLHK-WJDWOHSUSA-N
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| InChi Code |
InChI=1S/C19H21NO/c1-20-12-6-11-16-15-8-3-2-7-14(15)13-19(21)18-10-5-4-9-17(16)18/h2-5,7-11,19-21H,6,12-13H2,1H3/b16-11-
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| Chemical Name |
(2Z)-2-[3-(methylamino)propylidene]tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaen-9-ol
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| Synonyms |
(Z)10Hydroxy Nortriptyline; (Z) 10 Hydroxy Nortriptyline
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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 |
| 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) |
DMSO: ~50 mg/mL (~179.0 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (8.95 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (8.95 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5794 mL | 17.8968 mL | 35.7935 mL | |
| 5 mM | 0.7159 mL | 3.5794 mL | 7.1587 mL | |
| 10 mM | 0.3579 mL | 1.7897 mL | 3.5794 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.
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