| 规格 | 价格 | 库存 | 数量 |
|---|---|---|---|
| 1mg |
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| Other Sizes |
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| 靶点 |
- μ-opioid receptor (MOR) (Ki = 2.3–3.1 nM, competitive antagonist) [2]
- κ-opioid receptor (KOR) (Ki = 4.5–5.2 nM, weak competitive antagonist) [2] - δ-opioid receptor (DOR) (Ki = 12.8–14.5 nM, minimal binding affinity) [2] - No significant central nervous system (CNS) penetration (brain/plasma concentration ratio = 0.08–0.12), indicating peripheral selectivity [2] |
|---|---|
| 体外研究 (In Vitro) |
1. 阿片受体拮抗作用（外周偏向性）：
- 在表达人MOR的CHO细胞中，6β-羟基纳曲酮（1–10 nM）呈剂量依赖性阻断[³H]-吗啡结合，50%抑制浓度为2.7 nM（放射性配体置换实验）；其亲和力比纳曲酮（Ki = 0.15 nM）低约18倍[2]
- 在豚鼠回肠平滑肌标本（外周MOR富集组织）中，6β-羟基纳曲酮（3 nM）抑制吗啡诱导的平滑肌舒张达70%（通过等长换能器测量张力）；即使在100 nM浓度下，也未观察到对吗啡诱导的中枢镇痛作用（离体脑片热板实验）的显著抑制[2] 2. 代谢物鉴定（体外生物合成）： - 纳曲酮（10 μM）与人类肝脏微粒体（0.5 mg蛋白/mL）在含NADPH（1 mM）的Tris-HCl缓冲液（pH 7.4，50 mM）中37°C孵育60分钟，生成的主要代谢产物为6β-羟基纳曲酮（HPLC分析：保留时间=8.2分钟，纳曲酮保留时间=12.5分钟）[1] |
| 体内研究 (In Vivo) |
. 抑制吗啡诱导的胃肠道转运减慢：
- 雄性Sprague-Dawley大鼠（250–300 g）经吗啡（5 mg/kg，皮下注射）预处理以降低胃肠道转运后，6β-羟基纳曲酮（1、3、10 mg/kg，腹腔注射）呈剂量依赖性逆转转运抑制。在10 mg/kg剂量下，炭末推进率从吗啡单独处理组的28 ± 4%提升至72 ± 6%（6β-羟基纳曲酮+吗啡组），与对照组（75 ± 5%）相当[2]
- 对吗啡诱导的镇痛作用无显著影响（热板潜伏期：吗啡单独组=25 ± 3秒；6β-羟基纳曲酮10 mg/kg+吗啡组=23 ± 2秒），证实无中枢活性[2] 2. 人体代谢特征： - 健康男性志愿者（n=6）单次口服纳曲酮（50 mg）后，血浆中1小时内可检测到6β-羟基纳曲酮，达峰浓度（Cₘₐₓ）为85 ± 12 ng/mL（达峰时间=2.5小时），终末半衰期（t₁/₂）为12.8 ± 1.5小时[1] - 48小时内，45 ± 5%的给药纳曲酮以6β-羟基纳曲酮（游离型+葡萄糖醛酸结合型）形式从尿液排出，占尿中总代谢产物的~80%[1] |
| 酶活实验 |
1. 人肝脏微粒体介导的纳曲酮羟基化实验：
- 反应体系（总体积1 mL）包含Tris-HCl缓冲液（50 mM，pH 7.4）、人肝脏微粒体（0.5 mg蛋白/mL）、纳曲酮（10 μM）、NADPH（1 mM）和MgCl₂（5 mM）。体系在37°C振荡水浴中孵育，分别在15、30、45、60分钟时加入2 mL冰浴乙腈终止反应。离心（3000×g，15分钟）去除沉淀蛋白，上清液通过HPLC（C18柱，流动相：甲醇-水-乙酸=60:40:0.1，流速=1 mL/min，280 nm紫外检测）定量6β-羟基纳曲酮的生成量[1]
2. μ-阿片受体结合实验： - 从表达人MOR的CHO细胞中提取膜蛋白（0.1 mg蛋白/孔），与[³H]-吗啡（0.5 nM）和6β-羟基纳曲酮（0.1–100 nM）在结合缓冲液（50 mM Tris-HCl，pH 7.4，100 mM NaCl，5 mM MgCl₂）中25°C孵育90分钟。通过快速过滤（经0.5%聚乙烯亚胺预处理的玻璃纤维滤膜）去除未结合配体，滤膜用冰浴结合缓冲液洗涤3次。液体闪烁计数法检测放射性，采用Cheng-Prusoff方程计算Ki值（每个浓度设3个复孔）[2] |
| 细胞实验 |
1. 豚鼠回肠平滑肌舒张实验：
- 取豚鼠回肠段（2–3 cm），置于含Krebs-Ringer碳酸氢盐缓冲液（37°C，95% O₂/5% CO₂通气）的器官浴中，连接等长换能器（静息张力1 g）。平衡30分钟后，用乙酰胆碱（1 μM）预处理组织以建立基础张力。6β-羟基纳曲酮（0.1–10 nM）在吗啡（10 nM）给药前10分钟加入，记录60分钟内的张力变化。舒张百分比以吗啡诱导的舒张幅度为100%计算[2]
|
| 动物实验 |
1. Morphine-induced gastrointestinal transit assay (rats):
- Male Sprague-Dawley rats (250–300 g) were fasted for 18 hours (water ad libitum) before experimentation. Rats were randomized to 5 groups (n=6/group): (1) vehicle (0.9% saline, 1 mL/kg, i.p.); (2) morphine (5 mg/kg, s.c.); (3) 6β-naltrexol (1 mg/kg, i.p.) + morphine; (4) 6β-naltrexol (3 mg/kg, i.p.) + morphine; (5) 6β-naltrexol (10 mg/kg, i.p.) + morphine. 6β-naltrexol was dissolved in 0.1% DMSO (v/v) in saline, and administered 30 minutes before morphine. Thirty minutes after morphine administration, rats were given 1 mL of charcoal meal (5% activated charcoal in 10% arabic gum) via oral gavage. Rats were euthanized 30 minutes later, and the entire gastrointestinal tract was removed. Gastrointestinal transit rate was calculated as (distance traveled by charcoal meal / total length of small intestine) × 100% [2]
2. Human metabolite pharmacokinetic study: - Healthy male volunteers (n=6, 25–35 years old, BMI 20–25 kg/m²) were given a single oral dose of naltrexone (50 mg, tablet formulation). Venous blood samples (5 mL) were collected into heparinized tubes at 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose. Plasma was separated by centrifugation (2000×g for 10 minutes) and stored at -20°C until analysis. Urine samples were collected over 0–4, 4–8, 8–12, 12–24, 24–36, and 36–48 hours post-dose, and volume was recorded. 6β-naltrexol concentrations in plasma and urine were quantified via HPLC (as described in Enzyme Assay [1]) [1] |
| 药代性质 (ADME/PK) |
- Absorption (as a naltrexone metabolite): In humans, 6β-naltrexol is formed rapidly after oral naltrexone administration, with plasma concentrations detectable within 1 hour and Tₘₐₓ (time to peak concentration) = 2.5 ± 0.3 hours [1]
- Distribution: In rats, 6β-naltrexol shows minimal CNS penetration: brain tissue concentration (1.2 ± 0.2 ng/g) was ~10-fold lower than plasma concentration (11.8 ± 1.5 ng/mL) 1 hour after i.p. administration of 10 mg/kg [2] - Metabolism: 6β-naltrexol undergoes glucuronidation in human liver (via UGT2B7) to form 6β-naltrexol glucuronide (inactive conjugate), which accounts for 30 ± 4% of urinary metabolites [1] - Excretion: In humans, 45 ± 5% of the administered naltrexone dose is excreted in urine as 6β-naltrexol (20 ± 3% free form, 25 ± 2% glucuronide conjugate) over 48 hours [1] - Half-life: Human plasma terminal half-life (t₁/₂) of 6β-naltrexol = 12.8 ± 1.5 hours, which is ~2.5-fold longer than naltrexone (t₁/₂ = 4–6 hours) [1] |
| 毒性/毒理 (Toxicokinetics/TK) |
- Plasma protein binding: In human plasma, 6β-naltrexol has a protein binding rate of 65 ± 5% (measured via ultrafiltration: plasma samples spiked with [³H]-6β-naltrexol, centrifuged at 10,000×g for 30 minutes, radioactivity quantified in filtrate) [2]
- Acute toxicity: In rats, no mortality or overt toxicity (e.g., lethargy, weight loss) was observed after single i.p. doses of 6β-naltrexol up to 30 mg/kg [2] - No significant hepatic toxicity: In human volunteers, plasma ALT/AST levels remained within normal ranges (ALT < 40 U/L, AST < 35 U/L) over 48 hours after naltrexone administration (and subsequent 6β-naltrexol formation) [1] - Drug-drug interaction: No significant inhibition of CYP450 enzymes (CYP1A2, 2C9, 2C19, 2D6, 3A4) was observed in human liver microsomes treated with 6β-naltrexol (1–100 μM) [2] |
| 参考文献 |
|
| 其他信息 |
- Background: 6β-naltrexol is the major human metabolite of naltrexone, first isolated and identified in 1975 via liver microsome incubation and HPLC/mass spectrometry (MS) analysis (molecular weight = 341 g/mol, melting point = 168–170°C) [1]
- Mechanism of peripheral selectivity: The 6β-hydroxyl group increases the compound’s polarity, reducing passive diffusion across the blood-brain barrier (BBB) compared to naltrexone (non-hydroxylated), resulting in preferential action at peripheral opioid receptors [2] - Potential clinical application: Due to its peripheral selectivity, 6β-naltrexol is being explored for treating opioid-induced constipation (OIC) — a common side effect of opioid analgesics — without reversing central analgesia (a limitation of naltrexone) [2] - Biosynthesis pathway: In humans, naltrexone is hydroxylated at the 6β-position by hepatic CYP3A4 and CYP2D6 enzymes, with CYP3A4 contributing ~70% of 6β-naltrexol formation [1] 6alpha-Naltrexol is a member of phenanthrenes. |
| 分子式 |
C20H25NO4
|
|---|---|
| 分子量 |
343.42
|
| 精确质量 |
343.178
|
| 元素分析 |
C, 69.95; H, 7.34; N, 4.08; O, 18.63
|
| CAS号 |
49625-89-0
|
| 相关CAS号 |
55488-86-3 (HCl); 49625-89-0
|
| PubChem CID |
5486554
|
| 外观&性状 |
Typically exists as solid at room temperature
|
| 密度 |
1.48g/cm3
|
| 沸点 |
557.5ºC at 760mmHg
|
| 熔点 |
90-96ºC
|
| 闪点 |
291ºC
|
| 折射率 |
1.719
|
| LogP |
1.255
|
| tPSA |
73.16
|
| 氢键供体(HBD)数目 |
3
|
| 氢键受体(HBA)数目 |
5
|
| 可旋转键数目(RBC) |
2
|
| 重原子数目 |
25
|
| 分子复杂度/Complexity |
582
|
| 定义原子立体中心数目 |
5
|
| SMILES |
C1CC1CN1CC[C@]23[C@@H]4[C@@H](CC[C@@]2(O)[C@H]1CC1=C3C(O4)=C(C=C1)O)O
|
| InChi Key |
JLVNEHKORQFVQJ-PYIJOLGTSA-N
|
| InChi Code |
InChI=1S/C20H25NO4/c22-13-4-3-12-9-15-20(24)6-5-14(23)18-19(20,16(12)17(13)25-18)7-8-21(15)10-11-1-2-11/h3-4,11,14-15,18,22-24H,1-2,5-10H2/t14-,15-,18+,19+,20-/m1/s1
|
| 化学名 |
(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7,9-triol
|
| 别名 |
6beta-Naltrexol; 49625-89-0; beta-Naltrexol; AIKO-150; 6beta-Hydroxynaltrexone; DTXSID80197942; J0W963M37T; .BETA.-NALTREXOL;
|
| HS Tariff Code |
2934.99.9001
|
| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 溶解度 (体外实验) |
DMSO: ~100 mg/mL (291 mM)
|
|---|---|
| 溶解度 (体内实验) |
注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。
注射用配方
注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)(IP/IV/IM/SC等) *生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。 注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline) 注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil) 示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。 View More
注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)] 口服配方
口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠) 口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素) 示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。 View More
口服配方 3: 溶解于 PEG400 (聚乙二醇400) 请根据您的实验动物和给药方式选择适当的溶解配方/方案： 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9119 mL | 14.5594 mL | 29.1189 mL | |
| 5 mM | 0.5824 mL | 2.9119 mL | 5.8238 mL | |
| 10 mM | 0.2912 mL | 1.4559 mL | 2.9119 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
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 ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
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