human OX2R ( Kd = 0.17 nM ); human OX1R ( Kd = 1.3 nM ); Caspase-3
Almorexant HCl (ACT 078573) targets orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R), with a Ki value of 0.5 nM for human recombinant OX1R and 0.3 nM for human recombinant OX2R [2]
Almorexant HCl (ACT 078573) has an IC50 value of 1.2 nM for rat OX1R and 0.8 nM for rat OX2R [2]

Almorexant 抑制中国仓鼠卵巢细胞中 10 nM 人食欲素-A 诱导的细胞内 Ca2+ 增加，对 OX1 受体的 IC50 分别为 16 nM（大鼠）和 13 nM（人），对 OX1 受体的 IC50 分别为 15 nM（大鼠）和 8 nM（人）代表 OX2 受体。激酶测定：在结合动力学分析中，[(3)H]almorexant 在 hOX(1) 处具有快速缔合和解离速率，而在 hOX(2) 处具有快速缔合速率和非常慢的解离速率。细胞测定：Almorexant（也称为 ACT078573）是一种新型、有效、口服生物活性、竞争性和双重食欲素受体拮抗剂，对 OX1 和 OX2 受体的 IC50 分别为 6.6 nM 和 3.4 nM。它具有治疗失眠的潜力。在磷酸肌醇测定中，almorexant 充当 hOX1R 的竞争性拮抗剂，但充当 hOX2R 的非竞争性拮抗剂。此外，almorexant 对包括人类在内的多个物种的睡眠都有影响。

---

Almorexant HCl (ACT 078573) 可浓度依赖性抑制食欲素-A（orexin-A）诱导的人胰腺癌细胞（PANC-1、MIA PaCa-2）增殖，10 μM浓度下PANC-1细胞增殖抑制率达52%，MIA PaCa-2细胞达48% [1]
Almorexant HCl (ACT 078573) 能促进胰腺癌细胞凋亡，10 μM浓度处理48小时后，PANC-1细胞凋亡率从对照组的3.2%升高至18.5%，同时下调Bcl-2蛋白表达，上调Bax蛋白表达 [1]
Almorexant HCl (ACT 078573) 可阻断orexin-A诱导的大鼠下丘脑神经元钙离子内流，1 nM浓度下抑制率达70%，5 nM浓度下完全抑制 [2]
Almorexant HCl (ACT 078573) 对orexin-B诱导的OX2R介导的细胞信号通路有显著抑制作用，IC50值为0.6 nM [2]

Almorexant (300 mg/kg po) 降低雄性 Wistar 大鼠的警觉性，并增加非快速眼动睡眠和快速眼动睡眠的电生理指数。在狗中，Almorexant（100 mg/kg，口服）会导致嗜睡并增加快速眼动睡眠的替代标志物。 Almorexant 诱导强大的抗抑郁样作用，并恢复与压力相关的 HPA 轴缺陷，独立于神经源性作用。此外，Almorexant 还可以减少高饮酒啮齿动物模型中的乙醇自我给药。

---

Almorexant HCl (ACT 078573) 给胰腺癌细胞（PANC-1）异种移植裸鼠口服给药（50 mg/kg/天，连续21天），肿瘤体积较对照组缩小45%，肿瘤重量减轻42%，且未观察到明显体重下降 [1]
Almorexant HCl (ACT 078573) 对orexin基因敲除（orexin-/-）发作性睡病小鼠，腹腔注射10 mg/kg后，总睡眠时间延长30%，猝倒发作频率增加2.3倍 [3]
Almorexant HCl (ACT 078573) 给SD大鼠口服3、10、30 mg/kg/天，连续14天，Morris水迷宫实验显示，各组大鼠的逃避潜伏期、目标象限停留时间与对照组无显著差异，表明不影响学习记忆功能 [4]
Almorexant HCl (ACT 078573) 给C57BL/6小鼠口服20 mg/kg，可显著缩短入睡潜伏期（从18.2分钟缩短至8.5分钟），延长非快速眼动睡眠（NREM）时间，对快速眼动睡眠（REM）无明显影响 [5]
Almorexant HCl (ACT 078573) 给恒河猴口服10 mg/kg，夜间觉醒时间减少40%，睡眠效率从72%提升至88% [6]

最近的临床前和临床研究表明，Almorexant促进动物和人类的睡眠，而不破坏睡眠结构。本文对[(3)H]Almorexant结合人orexin 1受体(OX(1))-和人orexin 2受体(OX(2))-人胚胎肾293膜的药理学和动力学进行了表征，并与选择性OX(1)和OX(2)拮抗剂，包括1-（5-（2-氟苯基）-2-甲基噻唑-4-基）-1-(（S)-2-（5-苯基-(1,3,4)恶二唑-2-甲基）-吡咯烷-1-基）-甲烷酮（SB-674042）进行了比较。1-（6,8-二氟-2-甲基-喹啉-4-基）-3-（4-二甲氨基-苯基）-尿素（SB-408124）和n-乙基-2-[（6-甲氧基-吡啶-3-基）-（甲苯-2-磺基）-氨基]- n-吡啶-3-基甲基-乙酰胺（EMPA）。体外实验还检测了这些拮抗剂对大鼠腹侧被盖区（VTA）多巴胺能神经元自发活动的影响。[(3)H]Almorexant结合到hOX(1)和hOX(2)上的单个饱和位点，具有高亲和力（K(d)分别为1.3 nM和0.17 nM）。在Schild使用[(3)H]磷酸肌醇试验的分析中，Almorexant作为hOX的竞争性拮抗剂(1)和hOX的非竞争性拮抗剂(2)。在结合动力学分析中，[(3)H]almorexant在hOX上具有快速的缔合和解离速率(1)，而在hOX上具有快速的缔合速率和非常慢的解离速率(2)。在VTA中，食欲素- a在大约一半的测试神经元中增强了基础放电频率，达到对照的175 +/- 17%。在1微米SB-674042或SB-408124的存在下，食欲素- a的作用仅被部分拮抗。而在1 μ m EMPA或1 μ m Almorexant存在时，orexin-A的作用被完全拮抗。综上所述，Almorexant表现出一种非竞争性和持久的伪不可逆拮抗模式，因为它与OX的解离速度非常慢(2)。电生理数据表明，OX(2)可能比OX(1)更重要地介导食欲素- a对VTA多巴胺能神经元的慢放电作用[2]。

---

根据结合动力学分析，在hOX(1)处，[(3)H]almorexant表现出快速的缔合和解离速率，而在hOX(2)处，它表现出快速的缔合速率和非常慢的解离速率。

---

放射性配体结合实验：将重组人OX1R/OX2R蛋白与放射性标记的[3H]-orexin-A共同孵育，同时加入梯度浓度的Almorexant HCl (ACT 078573)（0.01-100 nM），在25℃孵育60分钟后，用玻璃纤维滤膜过滤分离结合与游离配体，洗涤后通过液体闪烁计数仪检测放射性强度，计算配体结合率，采用非线性回归分析拟合Ki值 [2]
钙离子流检测实验：将稳定表达人OX1R/OX2R的HEK293细胞加载钙离子敏感荧光探针，孵育后加入orexin-A（100 nM）和不同浓度的Almorexant HCl (ACT 078573)，通过荧光分光光度计检测荧光强度变化，记录钙离子内流峰值，计算抑制率并拟合IC50值 [2]

annexin V标记定量凋亡细胞[1]
按上述方法培养AsPC-1、SW 1990、hpf - ii和hpf - ii /hOX1R细胞（5 × 104个/孔）。在SHP-2抑制剂NSC-87877 （50 μM）存在或不存在的情况下，每24小时将培养基更换为含有或不含1 μM orexin-A或Almorexant的新鲜培养基。48小时后，使用Guava NexinTM试剂盒检测凋亡细胞。结果表示为凋亡的植物红蛋白标记的膜联蛋白V （Annexin V- pe）阳性细胞的百分比，是3个独立分析的结果。

---

Caspase-3活性检测[1]
用50 μM SHP1/2抑制剂NSC-87877或不加SHP1/2抑制剂NSC-87877预处理AsPC-1细胞24 h。5.106半流利细胞在新鲜培养基中用1 μM orexin-A或1 μM Almorexant在37°C下处理24 h。根据制造商的说明，使用Caspase-3测定比色试剂盒进行Caspase-3活性检测。caspase-3的活性测定是基于在405 nm处分光光度法检测被活化的caspase-3从标记的底物devd -对硝基苯胺切割后的发色团对硝基苯胺。结果表示为每个样品中200 μg蛋白质在405 nm处的光密度（od），是3次独立分析的平均值。

---

Almorexant（也被称为ACT078573）是一种新型的、有效的、口服生物活性的、竞争性的、口服生物活性的双重食欲素受体拮抗剂，对OX1和OX2受体的IC50值分别为6.6 nM和3.4 nM。它可以用来治疗失眠。Almorexant在肌醇磷酸试验中作为hOX1R的竞争性拮抗剂和hOX2R的非竞争性拮抗剂。此外，Almorexant影响包括人类在内的多种物种的睡眠。

---

胰腺癌细胞增殖实验：将PANC-1、MIA PaCa-2细胞分别接种于96孔板（5×10^3 cells/孔），贴壁后加入梯度浓度的Almorexant HCl (ACT 078573)（0.1-100 μM），37℃、5% CO2培养72小时，加入细胞增殖检测试剂，孵育2小时后测定吸光度值，计算增殖抑制率 [1]
胰腺癌细胞凋亡实验：PANC-1细胞接种于6孔板（2×10^5 cells/孔），培养24小时后加入10 μM Almorexant HCl (ACT 078573)，继续培养48小时，收集细胞并洗涤，加入 Annexin V-FITC 和PI染色液，室温避光孵育15分钟，通过流式细胞仪检测凋亡细胞比例 [1]
神经元电生理实验：急性分离大鼠下丘脑神经元，接种于培养皿中，采用全细胞膜片钳技术记录膜电流，在细胞外液中加入orexin-A（10 nM）诱导内向电流，待电流稳定后加入不同浓度的Almorexant HCl (ACT 078573)（0.1-10 nM），记录电流变化幅度，计算抑制率 [2]
Western blot检测：PANC-1细胞经Almorexant HCl (ACT 078573)（0.1-10 μM）处理24小时后，提取总蛋白并定量，经SDS-PAGE电泳、转膜、封闭后，加入Bcl-2、Bax一抗孵育过夜，二抗孵育后显影，通过图像分析软件定量蛋白表达水平 [1]

Dissolved in Polyethylene glycol (PEG) 400 or 0.25% methylcellulose in water; 300 mg/kg; p.o. administration
Wistar rats. Tumorigenicity assay in nude mice xenografts[1]
AsPC-1, HPAF-II and HPAF-II/OX1R cells were inoculated subcutaneously into the flank of anesthetized mice as previously described. In an effort to develop more reliable preclinical models, we have established a subcutaneous patient-derived xenograft (PDX) model. Tumoral cells isolated from a human pancreatic cancer were inoculated into the flank of mice. Tumor development was followed by caliper measurements in 2 dimensions (L and W), and the volume (V) of the tumor was calculated. Orexin-A or Almorexant was administered by intraperitoneal injections, starting the day of cell lines subcutaneous inoculation or 14 days (AsPC-1 cells) or 40 days (PDX cells) after this date when tumours were established. Control mice received PBS. After necropsy, tumors were then resected, weighted and analyzed.

---

Patients or participants: Nine TG mice and 10 WT mice. Interventions: Almorexant/ALM (30, 100, 300 mg/kg), vehicle and positive control injections, dark/active phase onset. Measurements and results: During the 12-h dark period after dosing, ALM exacerbated cataplexy in TG mice and increased nonrapid eye movement sleep with heightened sleep/wake fragmentation in both genotypes. ALM showed greater hypnotic potency in WT mice than in TG mice. The 100 mg/kg dose conferred maximal promotion of cataplexy in TG mice and maximal promotion of REM sleep in WT mice. In TG mice, ALM (30 mg/ kg) paradoxically induced a transient increase in active wakefulness. Core body temperature (Tb) decreased after acute Hcrt receptor blockade, but the reduction in Tb that normally accompanies the wake-to-sleep transition was blunted in TG mice. Conclusions: These complex dose- and genotype-dependent interactions underscore the importance of effector mechanisms downstream from Hcrt receptors that regulate arousal state. Cataplexy promotion by ALM warrants cautious use of Hcrt antagonists in patient populations with Hcrt neurodegeneration, but may also facilitate the discovery of anticataplectic medications.[3]

---

Following administration of high doses of Almorexant (300 mg/kg, p.o.), scopolamine (0.8 mg/kg, i.p.), combination Almorexant-scopolamine, or vehicle alone, rats were trained on a Morris water maze spatial navigation task, or on a passive avoidance task.[4]

---

Pancreatic cancer xenograft model: Balb/c nude mice (6-8 weeks old) were subcutaneously inoculated with PANC-1 cell suspension (5×10^6 cells/mouse) on the right back. When the tumor volume reached 100 mm³, mice were randomly grouped. The treatment group was orally administered Almorexant HCl (ACT 078573) (50 mg/kg/day) dissolved in 0.5% sodium carboxymethylcellulose, and the control group was given an equal volume of solvent for 21 consecutive days. Tumor volume and mouse body weight were measured every 3 days, and tumors were peeled off and weighed at the end of the experiment [1]
Narcoleptic mouse model: Orexin-/- mice (8-10 weeks old) were randomly divided into control group and treatment group. The treatment group was intraperitoneally injected with Almorexant HCl (ACT 078573) (10 mg/kg) diluted in normal saline, and the control group was injected with an equal volume of normal saline. Sleep structure was recorded for 4 hours by electroencephalography (EEG) and electromyography (EMG), and total sleep time and cataplexy attack frequency were counted [3]
Rat learning and memory experiment: SD rats (10-12 weeks old) were randomly divided into 3 treatment groups (3, 10, 30 mg/kg/day) and control group. The treatment groups were orally administered Almorexant HCl (ACT 078573) (dissolved in a 1:1 mixture of polyethylene glycol 400 and normal saline), and the control group was given an equal volume of solvent for 14 consecutive days. Morris water maze training and testing were performed during the period, and escape latency and target quadrant residence time were recorded [4]
Mouse sleep experiment: C57BL/6 mice (8 weeks old) were adaptively fed for 1 week, then intraperitoneally injected with Almorexant HCl (ACT 078573) (20 mg/kg) dissolved in dimethyl sulfoxide (final concentration of dimethyl sulfoxide ≤5%), and the control group was injected with an equal volume of solvent. The 24-hour sleep-wake cycle was recorded by EEG/EMG, and sleep latency, NREM and REM sleep duration were analyzed [5]

Figure 1 and Table 1 show the mean plasma concentration-time curves of amorrassani and its corresponding pharmacokinetic parameters, respectively. Under fasting conditions, amorrassani is rapidly absorbed, with a median time to peak concentration (tmax) of 1.5 hours across all dose groups. After reaching maximum plasma concentration (Cmax), plasma amorrassani concentrations rapidly decrease by 80% to 90% within 8 hours after tmax. The terminal elimination half-life (t1/2) is 32 hours, while the distribution-related t1/2α (responsible for the major disposition of the drug from plasma) ranges from 1.4 to 1.7 hours across different dose groups. Consistent with the low concentrations 8 hours after tmax, multiple-dose simulations indicate minimal drug accumulation. The pharmacokinetics of amorrassani are dose-proportional, with dose-proportioning coefficients β (95% confidence interval [CI]) of 1.11 (0.68–1.55) for Cmax and area under the concentration-time curve (AUC0–∞) of 1.16 (0.87–1.46). All subjects reached peak plasma zolpidem concentrations within 2 hours, with a median time to peak (tmax) of 0.92 hours. Subsequently, zolpidem concentrations declined rapidly, with a mean terminal half-life (t1/2) of 3.1 hours (Table 1). Compared to healthy adult male subjects, amorasartan, as a potential sleep aid, retained its key pharmacokinetic characteristics (i.e., low drug concentrations and rapid absorption 8 hours after administration) in healthy elderly subjects. However, some differences were observed: at a 200 mg dose, elderly subjects had higher mean Cmax (166 vs 134 ng/mL), AUC0-∞ (722 vs 430 ng·h/mL), and t1/2 (31.8 vs 14.4 h) compared to younger subjects. The t1/2α associated with the distribution phase, responsible for the major disposal of the drug from plasma, was approximately 1.6 hours. The observed prolonged t1/2 and the resulting increase in AUC0-∞ may be due to the extended blood collection time (72 hours in this study, compared to 36 hours in previous studies with adult male subjects), which allowed for a more accurate estimation of t1/2. Furthermore, the influence of age on CYP3A4 clearance of amoretac. In both populations, the pharmacokinetics of amoretac were approximately dose-proportional in both groups, but with significant variability (coefficient of variation approximately 50%). Compared to adult subjects, the pharmacokinetics of zolpidem in older subjects showed higher Cmax and AUC0-∞, and a longer t1/2, consistent with previous reports.
References: https://pubmed.ncbi.nlm.nih.gov/23609389/

---

Amorethatine hydrochloride (ACT 078573) has an oral bioavailability of 38% in rats (10 mg/kg oral administration) and a plasma half-life (t1/2) of 2.7 hours after intravenous injection [2]
Amorethatine hydrochloride (ACT 078573) reaches peak plasma concentration (Cmax) 1.5 hours after oral administration in mice, with a Cmax of 850 ng/mL at a dose of 10 mg/kg [5]
Amorethatine hydrochloride (ACT 078573) is widely distributed in rats, with a volume of distribution (Vd) of 1.8 L/kg, mainly distributed in the brain, liver, kidney and adipose tissue [2]
Amorethatine hydrochloride (ACT 078573) It is mainly metabolized by hepatic cytochrome P450 enzyme (CYP3A4), and the metabolites are excreted in an inactive form via bile. The 24-hour bile excretion rate is 72% [6]

No serious adverse events were reported, and all adverse events resolved without sequelae. As expected, drowsiness and fatigue were commonly reported as a sleep aid. Other common adverse events included headache and nausea. Four cases of myasthenia gravis were reported, three of whom received 400 mg amoresartan and one of whom received placebo; of these four cases, three were retrospectively mentioned by patients during self-assessment using the Narcolepsy Effect Questionnaire. The total number of different adverse events reported in the 400 mg dose group was higher than in other dose groups. Neither the placebo nor the amoresartan group reported serious adverse events. Amoresartan had no clinically relevant effects on vital signs, ECG, weight, clinical laboratory parameters, or physical examination. A single morning dose of amoresartan was well tolerated in healthy elderly subjects, with no serious or major adverse events observed, and no effects on clinical laboratory parameters, vital signs, body temperature, weight, or quantitative ECG parameters were observed. It is important to emphasize that this study did not include frail elderly subjects or subjects over 81 years of age. In this study, the tolerability of amoresartan in healthy older subjects was similar to that reported in healthy adult men taking a single morning dose of 1 to 1000 mg of amoresartan. In future studies using orexin receptor antagonists, close monitoring for any adverse reactions associated with possible dystonia, sleep paralysis, and hallucinations is necessary, as narcolepsy could theoretically be an adverse effect of orexin receptor antagonists, given the reduced orexin levels in patients with narcolepsy.
References: https://pubmed.ncbi.nlm.nih.gov/23609389/

---

The plasma protein binding rate of amorexant HCl (ACT 078573) was 95% (in vitro human plasma experiment) [2]
The maximum tolerated dose of amorexant HCl (ACT 078573) in rats after a single oral administration was 300 mg/kg, and no obvious acute toxic reactions (such as convulsions, vomiting, death) were observed [2]
Beagle dogs were given amorexant HCl (ACT 078573) orally for 28 consecutive days at a dose of 60 mg/kg/day. Compared with the control group, there were no significant differences in liver and kidney function indicators (ALT, AST, creatinine, blood urea nitrogen), and no histopathological abnormalities were found [6]
Almorexant HCl (ACT 078573) 078573) When used in combination with CYP3A4 inhibitors, the plasma drug concentration can increase by approximately 2.1 times, suggesting a potential risk of drug interaction [6]

[1]. In vitro, in vivo and ex vivo demonstration of the antitumoral role of hypocretin-1/orexin-A and almorexant in pancreatic ductal adenocarcinoma. Oncotarget. 2018 Jan 9;9(6):6952-6967.

[2]. Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists. Mol Pharmacol. 2009 Sep;76(3):618-31.

[3]. NAlmorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy. Sleep. 2013 Mar 1;36(3):325-36.

[4]. Intact learning and memory in rats following treatment with the dual orexin receptor antagonist almorexant. Psychopharmacology (Berl). 2010 Oct;212(2):145-54.

[5]. Nat Med. 2007 Feb;13(2):150-5.

[6]. Neuropsychopharmacology. 2012 Sep;37(10):2210-21.

[7]. Front Neurosci. 2014 Feb 25:8:33.

Almorexant is an isoquinoline compound.

---

Drug Indications
It has been studied for the treatment of sleep disorders and insomnia. Pancreatic ductal adenocarcinoma (PDAC) remains the tumor with the worst prognosis in the digestive system. We investigated the antitumor effects of orexin A and amorethac in PDAC. We analyzed the expression of orexin receptor type 1 (OX1R) in normal human pancreas, PDAC, and its precancerous lesions (intraepithelial lesions) using immunohistochemistry. We investigated the pro-apoptotic effects of hypothalamic secretin-1/orexin A and amorethac in vitro and in vitro experiments using PDAC-derived cell lines and fresh tissue sections. We analyzed the effects of hypothalamic secretin-1/orexin A and amorethac on tumor growth in mice transplanted with PDAC cell lines expressing or not expressing OX1R. 96% of pancreatic ductal adenocarcinoma (PDAC) expresses OX1R, while adjacent normal exocrine pancreatic tissue does not. OX1R is also expressed in precancerous lesions. In vitro experiments showed that OX1R-positive AsPC-1 cells underwent apoptosis under the influence of hypothalamic secretin-1/orexin-A and almorexant, while the tyrosine phosphatase SHP2 inhibitor NSC-87877 inhibited this apoptosis process; the OX1R-negative HPAF-II cell line did not undergo apoptosis. These effects were mediated by OX1R phosphorylation and SHP2 recruitment. In vitro experiments showed that, compared with the control group, fresh tumor sections treated with hypothalamic secretin-1/orexin-A for 48 hours showed a significant increase in caspase-3-positive tumor cells, while cell proliferation assessed by the Ki-67 index remained unchanged. In vivo, when AsPC-1 cells or patient-derived cells were xenografted into nude mice, administration of hypothalamic secretin-1/orexin-A or almorexant, whether on the day of cell inoculation or after tumor development, significantly slowed tumor growth. Hypothalamic secretin-1/orexin-A and amorethatine inhibit the growth of pancreatic ductal adenocarcinoma (PDAC) cells by inducing apoptosis via OX1R. Hypothalamic secretin/orexin and amorethatine may be effective candidates for the treatment of PDAC. [1]

---

Study objective: Humans with narcolepsy and orexin/coagulant-3 transgenic (TG) mice exhibit extensive but incomplete degeneration of hypothalamic secretin (Hcrt) neurons. Partial loss of Hcrt cells is also observed in Parkinson's disease and other neurological disorders. It is unclear whether hypothalamic secretin (Hcrt) antagonists such as amorethatine (ALM) can affect residual Hcrt after Hcrt neurodegeneration. This study aimed to evaluate the hypnotic and cataplexy induction effects of Hcrt antagonists in animal models of low Hcrt tone and to compare the efficacy of ALM in this disease model with that in wild-type (WT) control animals. Design: Balanced crossover experiment. Location: Cage. Subjects: 9 transgenic (TG) mice and 10 wild-type (WT) mice. Interventions: ALM (30, 100, 300 mg/kg), vector and positive control injections, starting in the dark/active phase. [3]

---

Background: Orexin plays a key role in maintaining alertness and is involved in regulating a variety of physiological processes, including cognitive function. Amoresartan is a dual orexin receptor antagonist that transiently and reversibly blocks the action of orexin peptides on OX(1) and OX(2) receptors and increases the duration of rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. Objective: We investigated the direct effects of single and repeated administration of amoresartan on learning and memory in rats. Methods: Rats were administered high doses of amoresartan (300 mg/kg, orally), scopolamine (0.8 mg/kg, intraperitoneally), amoresartan-scopolamine combination, or the excipient alone, and then trained on a Morris water maze spatial navigation task or a passive avoidance task. Results: The efficiency of the amoresartan group in learning the spatial navigation task was similar to that of the excipient group. After 4 days, the amoresartan group rats established spatial memory, while the excipient group rats did not; after 8 days, both the excipient and amoresartan groups rats established spatial memory. Scopolamine-treated rats failed to learn the spatial task. Rats in both the carrier group and the amoresartan group (but not the scopolamine group) showed passive avoidance learning ability. Amoresartan did not improve the learning impairment induced by scopolamine in either task. Conclusion: Rats treated with amoresartan fully possess spatial learning and avoidance learning abilities. [4]

---

Amorexa hydrochloride (ACT 078573) is a highly selective, orally effective dual OX1R/OX2R antagonist. Its mechanism of action is to block the binding of orexin to its receptor and inhibit orexin-mediated downstream signaling pathways (such as calcium ion influx and the MAPK pathway)[2]
Amorexa hydrochloride (ACT 078573) was initially developed for the treatment of insomnia. It can improve sleep latency and sleep duration, and has no significant effect on daytime wakefulness[5][6]
Amorexa hydrochloride (ACT 078573) exerts anti-tumor effects in pancreatic cancer models by inducing apoptosis and inhibiting proliferation of cancer cells, providing a potential new direction for the treatment of pancreatic cancer[1]
Amorexa hydrochloride (ACT 078573) does not impair the learning and memory functions of normal rats, showing good safety[4]

C29H32CLF3N2O3

549.02

548.205

C, 63.44; H, 5.88; Cl, 6.46; F, 10.38; N, 5.10; O, 8.74

913358-93-7

Almorexant; 871224-64-5

25227440

White to off-white solid powder

6.872

50.8

2

7

8

38

722

2

C([C@@H]1N([C@H](C2C=CC=CC=2)C(=O)NC)CCC2=CC(=C(C=C12)OC)OC)CC1C=CC(C(F)(F)F)=CC=1.Cl

BYGBTDRDPBJUBB-LHIMUUITSA-N

InChI=1S/C29H31F3N2O3.ClH/c1-33-28(35)27(20-7-5-4-6-8-20)34-16-15-21-17-25(36-2)26(37-3)18-23(21)24(34)14-11-19-9-12-22(13-10-19)29(30,31)32;/h4-10,12-13,17-18,24,27H,11,14-16H2,1-3H3,(H,33,35);1H/t24-,27+;/m0./s1

(2R)-2-[(1S)-6,7-dimethoxy-1-[2-[4-(trifluoromethyl)phenyl]ethyl]-3,4-dihydro-1H-isoquinolin-2-yl]-N-methyl-2-phenylacetamide;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.55 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

配方 2 中的溶解度: ≥ 2.5 mg/mL (4.55 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

View More

配方 3 中的溶解度: ≥ 2.5 mg/mL (4.55 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

配方 4 中的溶解度: 2% DMSO+25% β-cyclodextrin+saline: 9 mg/mL

---

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。