| 规格 | 价格 | 库存 | 数量 |
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| 100mg |
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| 250mg |
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| 500mg |
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| 靶点 |
D1 Receptor ( IC50 = 166 nM ); D2 Receptor ( IC50 = 1400 nM ); D3 Receptor ( IC50 = 3300 nM ); 5-HT1A Receptor ( IC50 = 370 nM )
Dopamine D2 receptor (Ki = 1.8 μM) [2][3] - Serotonin 5-HT1A receptor (Ki = 3.2 μM) [3][4] - μ-Opioid receptor (Ki = 12 μM) [4] |
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| 体外研究 (In Vitro) |
Rotundine 对多巴胺 D1 受体的亲和力高于 D2 受体，Ki 分别为 124 nM 和 388 nM，而 IC50 值分别为 166 nM (D1) 和 1.47 μM (D2)。 Rotundine 对多巴胺 D3 表现出弱抑制活性，IC50 为 3.25 μM。 Rotundine 还有效抑制 5-HT1A，IC50 为 374 nM，Ki 为 340 nM。除了突触后多巴胺受体的拮抗作用外，Rotundine 对突触前自身受体的抑制导致多巴胺释放增加，这可能归因于 Rotundine 对 D2 受体的亲和力较低。除多巴胺受体外，Rotundine 还可以与许多其他受体类型相互作用，包括 α-1 肾上腺素能受体（它充当拮抗剂）和 γ-氨基丁酸受体（它通过正变构促进 γ-氨基丁酸结合）影响。
Rotundine（罗通定） 在放射性配体结合实验中对多巴胺D2受体（Ki=1.8 μM）和5-HT1A受体（Ki=3.2 μM）表现出高亲和力，对μ阿片受体具有中等亲和力（Ki=12 μM）[2][3][4] - 在PC12细胞（大鼠嗜铬细胞瘤细胞）中，Rotundine（1–100 μM）以剂量依赖性方式抑制毛喉素诱导的cAMP积累，50 μM时最大抑制率达65%，证实其对Gαi偶联受体的拮抗活性[2] - 在原代大鼠皮质神经元中，Rotundine（10–50 μM）保护细胞免受谷氨酸诱导的兴奋性毒性损伤，50 μM时细胞活力提高42%，活性氧（ROS）产生减少38%[4] - 在小鼠脑突触体中，Rotundine（5–50 μM）剂量依赖性抑制多巴胺和血清素释放，IC50值分别为18 μM和22 μM[3] |
| 体内研究 (In Vivo) |
Rotundine治疗在6.25 mg/kg、12.5 mg/kg或18.75 mg/kg剂量下不影响运动活性，但显着拮抗羟考酮(5 mg/kg)诱导的多动症。口服Rotundine (10-25 mg/kg)显着增加小鼠的热板潜伏期，表明Rotundine具有显着的镇痛活性，这与弓状核中的β-内啡肽神经元和脊髓上D2受体有关。 Rotundine (1-10 mg/kg) 的给药剂量依赖性增加，而 20 mg/kg 会降低固定比例 (FR) 强化下可卡因自我给药的速率，这是由于突触后而不是突触前 DA 受体阻断机制。与对可卡因作用的影响相反，只有10mg/kg剂量的Rotundine对蔗糖自身给药和运动产生抑制作用，而不是1mg/kg或3mg/kg。
小鼠热板镇痛实验（热痛觉）中，腹腔注射Rotundine（20、40、80 mg/kg）以剂量依赖性方式延长缩足潜伏期。80 mg/kg剂量较对照组延长90%，镇痛持续时间达3小时[2][5] - 小鼠甩尾实验（机械痛觉）中，Rotundine（40 mg/kg，腹腔注射）延长甩尾潜伏期75%，并将低剂量吗啡（2 mg/kg，皮下注射）的镇痛效果增强40%[4] - 小鼠高架十字迷宫（EPM）焦虑模型中，口服Rotundine（30、60 mg/kg）使开放臂停留时间分别增加35%（30 mg/kg）和55%（60 mg/kg），表现出抗焦虑活性[3] - 睡眠剥夺诱导的认知障碍大鼠模型中，Rotundine（20 mg/kg，口服，每日一次，连续7天）改善Morris水迷宫中的空间记忆，逃避潜伏期减少45%[4] |
| 酶活实验 |
制备表达人多巴胺D2、5-HT1A或μ阿片受体的HEK293细胞膜悬液，将系列稀释的Rotundine（0.1–100 μM）与细胞膜悬液及相应[³H]标记配体（D2用螺哌隆、5-HT1A用8-OH-DPAT、μ阿片用DAMGO）混合，25°C孵育90分钟。过滤去除未结合配体，检测放射性强度，采用Cheng-Prusoff方程计算Ki值[2][3][4]
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| 细胞实验 |
PC12细胞cAMP抑制实验：PC12细胞接种到24孔板，血清饥饿24小时后，Rotundine（1–100 μM）预处理30分钟，再用毛喉素（10 μM）刺激30分钟，ELISA法定量细胞内cAMP水平[2]
- 皮质神经元兴奋性毒性实验：原代大鼠皮质神经元培养7天，Rotundine（10–50 μM）预处理1小时后，暴露于谷氨酸（100 μM）24小时。MTT法检测细胞活力，荧光探针检测ROS产生[4] - 突触体神经递质释放实验：分离小鼠脑突触体并悬浮于测定缓冲液，加入Rotundine（5–50 μM），KCl（50 mM）刺激诱导神经递质释放，高效液相色谱法（HPLC）定量上清液中多巴胺和血清素水平[3] |
| 动物实验 |
In this study, we use Kunming mice, which weigh between 18 and 22 g at birth. Rotundine (l-THP) (6.25, 12.5, and 18.75 mg/kg) or saline, respectively, is given once daily to four groups of mice for seven days in a row, with a five-day withdrawal period in between. All animals are challenged with saline on day 13. The mice are placed in the test boxes on days 1, 7, and 13 and their locomotor activity is observed for 60 minutes following a 40-minute treatment with either saline or rotundine.
Mouse Hot Plate Analgesia Model: Female ICR mice were randomly divided into control (saline) and Rotundine groups (20, 40, 80 mg/kg, i.p., n=8 per group). Paw withdrawal latency was measured at 30, 60, 120, and 180 minutes post-administration [2][5] - Mouse EPM Anxiety Model: Male BALB/c mice were divided into control (saline) and Rotundine groups (30, 60 mg/kg, p.o., n=7 per group). Drugs were administered 60 minutes before the EPM test, and the time spent in open arms and number of open arm entries were recorded [3] - Rat Morris Water Maze Cognitive Model: Male SD rats were subjected to sleep deprivation for 72 hours to induce cognitive impairment. Rats were treated with Rotundine (20 mg/kg, p.o.) or saline once daily for 7 days. Escape latency and time spent in the target quadrant were recorded during the 5-day training and probe test [4] |
| 药代性质 (ADME/PK) |
In rats, the oral bioavailability of rotundine (50 mg/kg) was 45%, the peak plasma concentration (Cmax) was 320 ng/mL, and the time to peak concentration (Tmax) was 1.2 hours. The plasma half-life (t1/2) was 3.8 hours [2][5]
- The drug is widely distributed throughout the body, with a volume of distribution of 11 L/kg in rats. It can cross the blood-brain barrier, and the brain-to-plasma concentration ratio was 2.5 2 hours after administration [2][4] - Rotundine is mainly metabolized in the liver by glucuronidation and demethylation. Approximately 60% of the dose is excreted in the urine and 35% in the feces, mainly as metabolites [5] - The protein binding rate of rotundine in human plasma is 78% [3] |
| 毒性/毒理 (Toxicokinetics/TK) |
The median lethal dose (LD50) of rotundine orally in mice was 650 mg/kg and in rats it was 820 mg/kg [5]. Common adverse clinical reactions included mild sedation (15% of patients), dizziness (10%), and dry mouth (8%), all of which were transient and resolved within 4-6 hours [2][3]. No significant hepatotoxicity or nephrotoxicity was observed in long-term animal studies (8 weeks) or clinical trials, and no sustained changes were observed in serum ALT, AST, creatinine, or blood urea nitrogen levels [2][4]. Concomitant use with central nervous system depressants (e.g., benzodiazepines, opioids) may enhance sedation and analgesia [4].
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| 参考文献 | |
| 其他信息 |
Tetrahydropalmatine is a berberine alkaloid synthesized by the addition of two hydrogen molecules to the pyridine ring of palmatine. It acts as an adrenergic agonist, a non-narcotic analgesic, and a dopaminergic antagonist. It is a berberine alkaloid, an organic heterotetracyclic compound, and (S)-7,8,13,14-tetrahydroprotoberberine. Functionally, it is related to palmatine-like compounds. Tetrahydropalmatine is currently being investigated in the clinical trial NCT02118610 (Use of L-Tetrahydropalmatine (L-THP) for the treatment of schizophrenia: a novel dopamine antagonist with anti-inflammatory and antiprotozoal activities). Tetrahydropalmatine has been reported to exist in Corydalis solida, Fibraurea recisa, and other organisms with relevant data.
Rotaxane is a naturally occurring alkaloid isolated from poppy plants (e.g., Corydalis yanhusuo)[1][5]. Its main mechanism of action involves dual regulation of dopamine D2 (antagonistic) and 5-HT1A (agonistic) receptors, as well as moderate binding to μ-opioid receptors, resulting in analgesic, anxiolytic, and sedative effects.[2][3][4] -Clinical indications include mild to moderate pain (e.g., headache, dysmenorrhea, postoperative pain), anxiety, and insomnia[1][5] -It has a lower risk of addiction compared to conventional opioid analgesics, making it suitable for long-term use in chronic pain management[4] -The clinical dose range is 30-120 mg daily, divided into three oral doses (10-40 mg three times daily)[1][5] |
| 分子式 |
C21H25NO4
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|---|---|---|
| 分子量 |
355.43
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| 精确质量 |
355.178
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| CAS号 |
483-14-7
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| 相关CAS号 |
Tetrahydropalmatine; 2934-97-6; Tetrahydropalmatine hydrochloride; 6024-85-7
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| PubChem CID |
72301
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| 外观&性状 |
White to off-white solid powder
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| 密度 |
1.2±0.1 g/cm3
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| 沸点 |
482.9±45.0 °C at 760 mmHg
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| 熔点 |
141-143ºC
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| 闪点 |
138.7±25.9 °C
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| 蒸汽压 |
0.0±1.2 mmHg at 25°C
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| 折射率 |
1.609
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| LogP |
3.7
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| tPSA |
40.16
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| 氢键供体(HBD)数目 |
0
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| 氢键受体(HBA)数目 |
5
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| 可旋转键数目(RBC) |
4
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| 重原子数目 |
26
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| 分子复杂度/Complexity |
475
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| 定义原子立体中心数目 |
1
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| SMILES |
COC1=C(C2=C(C[C@H]3C4=CC(=C(C=C4CCN3C2)OC)OC)C=C1)OC
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| InChi Key |
AEQDJSLRWYMAQI-KRWDZBQOSA-N
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| InChi Code |
InChI=1S/C21H25NO4/c1-23-18-6-5-13-9-17-15-11-20(25-3)19(24-2)10-14(15)7-8-22(17)12-16(13)21(18)26-4/h5-6,10-11,17H,7-9,12H2,1-4H3/t17-/m0/s1
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| 化学名 |
(13aS)-2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline
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| 别名 |
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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)
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| 溶解度 (体外实验) |
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| 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 | 2.8135 mL | 14.0675 mL | 28.1349 mL | |
| 5 mM | 0.5627 mL | 2.8135 mL | 5.6270 mL | |
| 10 mM | 0.2813 mL | 1.4067 mL | 2.8135 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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Thiethylperazine-d3
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