(E)-10-Hydroxynortriptyline
(Synonyms: E-10-OH-NT) 目录号 : GC60399
An active metabolite of amitriptyline and nortriptyline
Cas No.:47132-16-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
trans-10-hydroxy Nortriptyline is an active metabolite of the tricyclic antidepressants amitriptyline and nortriptyline .1,2 It is formed from amitriptyline and nortriptyline by the cytochrome P450 (CYP) isoform CYP2D6.1 trans-10-hydroxy Nortriptyline inhibits norepinephrine reuptake in rat cortical slices and isolated human plasma (EC50s = 160 and 176 nM, respectively).2
1.Coutts, R.T., Bach, M.V., and Baker, G.B.Metabolism of amitriptyline with CYP2D6 expressed in a human cell lineXenobiotica27(1)33-47(1997) 2.Bertilsson, l., Mellstr?m, B., and Sj?qvist, F.Pronounced inhibition of noradrenaline uptake by 10-hydroxymetabolites of nortriptylineLife Sci.25(15)1285-1292(1979)
| Cas No. | 47132-16-1 | SDF | |
| 别名 | E-10-OH-NT | ||
| Canonical SMILES | OC1C2=CC=CC=C2/C(C3=CC=CC=C3C1)=C/CCNC | ||
| 分子式 | C19H21NO | 分子量 | 279.38 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Studies on active transport of (E)-10-Hydroxynortriptyline in the kidney and brain of rats: effects of propranolol and quinidine
Pharmacol Toxicol 1991 May;68(5):380-3.PMID:1946183DOI:10.1111/j.1600-0773.1991.tb01256.x.
Studies in humans have given strong support of an active transport of (E)-10-Hydroxynortriptyline [E)-10-OH-NT) in the kidney and from the cerebrospinal fluid. After 3 days of intraperitoneal injections of (E)-10-OH-NT (10 mg/kg t.i.d.) in a rat model, we investigated the effect of propranolol and quinidine (25 and 2.5 mg/kg injected 6 times during day 3) on the concentrations of (E)-10-OH-NT in urine, plasma (total and unbound) and brain. In a group of control rats the renal clearance of (E)-10-OH-NT varied 10-fold between rats, but was reproducible from Day 2 to Day 3 (r = 0.83; n = 8; p less than 0.05). Quinidine markedly decreased the renal clearance of both total and unbound (E)-10-OH-NT from plasma, while the effect of propranolol was less pronounced. There was no difference in the ratio of (E)-10-OH-NT concentrations in brain and plasma (unbound) between treated and control rats. We conclude that (E)-10-OH-NT is actively secreted in the rat proximal tubule and that the activity of this system varies between rats, but is constant in the individual rat. Quinidine, and to a less extent propranolol, inhibits this renal secretion. By the present methodology we could not demonstrate an active transport of (E)-10-OH-NT from brain to blood in the rat. Studies using other methods are needed to further elucidate this.
Stereoselective efflux of (E)-10-Hydroxynortriptyline enantiomers from the cerebrospinal fluid of depressed patients
Pharmacol Toxicol 1991 Feb;68(2):100-3.PMID:1852713DOI:10.1111/j.1600-0773.1991.tb02044.x.
In 5 patients treated with nortriptyline or amitriptyline for at least 9 months, the cerebrospinal fluid (CSF)/plasma ratio for 10-hydroxynortriptyline (10-OH-NT) ranged from 0.085 to 0.172, which is similar to the ratio previously measured in patients treated for 3 weeks. In 4 other patients treated with racemic (E)-10-OH-NT, the mean concentration ratio between (-)- and (+)-(E)-10-OH-NT was 3.56 in plasma, 2.39 in plasma ultrafiltrate and 1.42 in CSF (one-way ANOVA; P less than 0.001). The mean free fraction in plasma determined by ultrafiltration for (-)-(E)-10-OH-NT was 28.9 +/- S.D.1.1% and for the (+)-enantiomer 43.7 +/- 0.8% (P less than 0.001) confirming the difference in protein binding shown previously in healthy subjects. There was a correlation between the concentration of 10-OH-NT (sum of enantiomers) in CSF and plasma ultrafiltrate (r = 0.96; n = 7; P less than 0.001). The concentration in CSF was, however, only about 50% of that in the plasma ultrafiltrate and this seems to be due to a stereoselective transport of (E)-10-OH-NT out from the CSF. The secretion from the CSF is more pronounced for the (-)-compared to the (+)-enantiomer, which is consistent with the stereoselectivity of the renal secretion of these compounds.
Treatment of depression with E-10-hydroxynortriptyline--a pilot study on biochemical effects and pharmacokinetics
Psychopharmacology (Berl) 1991;103(3):287-90.PMID:2057534DOI:10.1007/BF02244280.
The major metabolite of nortriptyline, i.E. E-10-hydroxynortriptyline (E-10-OH-NT), was given as a racemate in increasing doses from 75 to 225 mg/day to five patients with major depressive episode. Plasma concentrations of both the (-)- and (+)-enantiomers were linearly related to the doses. The mean ratio between them was 3.6 +/- 0.53, indicating stereospecific kinetics during maintenance treatment. Lumbar punctures were performed in four of the patients before and after 3 weeks of E-10-OH-NT treatment. There was a 18% mean decrease (P less than 0.01) in the noradrenaline metabolite HMPG in cerebrospinal fluid (CSF), supporting previous in vitro data showing that E-10-OH-NT inhibits noradrenaline uptake in vivo. During treatment, the median depression score measured by the Montgomery-Asberg Depression Rating Scale declined from 32 to 14 (P less than 0.05). As the study was open, the clinical outcome is not conclusive but does not contradict the hypothesis that E-10-OH-NT has antidepressant properties. If present at all, side effects were mild and did not interfere with the treatment.
Liquid-chromatographic determination of amitryptyline and its metabolites in serum, with adsorption onto glass minimized
Clin Chem 1982 Oct;28(10):2143-8.PMID:7127744doi
To study correlations between the concentrations, in serum, of amitriptyline and its most important metabolites with clinical response in patients, we developed a "high-performance" liquid-chromatographic method for routine determination of amitriptyline, nortriptyline, total 10-hydroxy-amitriptyline, desmethylnortriptyline, and E(trans)- and Z(cis)-10-Hydroxynortriptyline. These compounds are extracted from 1 mL of alkalinized serum into hexane/isoamyl alcohol (99/1 by vol). Perazine is the internal standard. To minimize irreversible adsorption of the drugs onto the glassware, 5 micrograms of maprotiline is added to the organic phase just before evaporation. After a 10-min resolution on a silica column eluted with acetonitrile/methanol/NH4OH (1 mol/L), absorbance is measured at 240 nm. Only chlorimipramine, doxepin, procainamide, and N-acetylprocainamide may interfere with assay of the compounds that probably are therapeutically relevant: amitriptyline, nortriptyline, and E-10-hydroxynortriptyline. Uremia, lipemia, and icterus also do not affect the analysis.