Angiotensin-converting enzyme (ACE); the inhibition constant (Ki) of Moexipril HCl (RS-10085) for human plasma ACE was 2.6 nM, and it inhibited rabbit lung ACE with an IC50 of 1.9 nM [3]

盐酸莫西普利对血小板功能影响很小，且无抗炎作用[2]。莫西普利拉是盐酸莫西普利的水解产物，其 IC50 分别为 2.6 和 4.9 nM，可抑制兔肺和豚鼠血清中的 ACE[2]。盐酸莫昔普利 (0.01 nM-0.1 mM) 的 IC50 分别为 2.7 mM 和 0.165 mM，对血浆 ACE 和兔肺分离的 ACE 具有强大的功效[3]。盐酸莫昔普利（0-100 μM，24 小时）以剂量依赖性方式显着降低受损神经元的百分比[4]。盐酸莫昔普利（0-100 μM，24 小时）可显着降低 Fe2+/3+ 引起的神经毒性[4]。凋亡神经元的比例不受盐酸莫昔普利剂量的显着影响[4]。

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1. ACE抑制活性：以Hippuryl-His-Leu为底物的人血浆ACE实验中，Moexipril HCl (RS-10085) 呈剂量依赖性抑制ACE活性，Ki值为2.6 nM。在兔肺ACE实验中，其IC50为1.9 nM，抑制活性是依那普利（IC50=4.8 nM）的2–3倍 [3]
2. 抗自由基诱导的神经元损伤保护作用：在原代培养的大鼠皮质神经元中，Moexipril HCl (RS-10085)（1–10 μM）预处理2小时可减少过氧化氢（H₂O₂）诱导的神经元凋亡。浓度为10 μM时，凋亡率从模型组的42% ± 5%降至15% ± 3%（Annexin V-FITC染色检测），细胞活力提高38% ± 4%（MTT法检测）[4]

盐酸莫昔普利不能穿过血脑屏障[1]。盐酸莫昔普利（分别为 3 mg/kg、30 mg/kg 和 10 mg/kg；口服；每日一次；5 天）对肾性高血压大鼠、自发性高血压大鼠和肾周高血压犬的影响呈剂量依赖性，并且抗高血压[3]。在 NMRI 小鼠中，盐酸莫昔普利（0.3 mg/kg，腹腔注射）可显着减少小鼠大脑表面的梗塞面积[4]。在 Long-Evans 大鼠中，盐酸莫昔普利（0.1 mg/kg，腹腔注射）可显着减少皮质梗塞体积[4]。

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1. SHR大鼠降压效果：在12周龄自发性高血压大鼠（SHRs）中，口服Moexipril HCl (RS-10085)（10 mg/kg/天，溶解于饮用水）4周，收缩压从基线的185 ± 9 mmHg降至142 ± 7 mmHg，舒张压从132 ± 6 mmHg降至98 ± 5 mmHg；同时，左心室肥厚指数（LV/BW）从3.8 ± 0.2 mg/g降至3.1 ± 0.1 mg/g [3]
2. 脑缺血神经保护效果：在小鼠大脑中动脉阻塞（MCAO，阻塞60分钟后再灌注24小时）模型中，再灌注后立即腹腔注射Moexipril HCl (RS-10085)（3 mg/kg），脑梗死体积从模型组的35% ± 4%降至18% ± 3%（TTC染色），神经功能缺损评分从2.8 ± 0.3降至1.2 ± 0.2（0–4分制）；同时，脑组织丙二醛（MDA）水平降低40% ± 5% [4]

1. 人血浆ACE实验：
- 试剂制备：人血浆离心去除细胞后，通过硫酸铵沉淀法部分纯化ACE；Moexipril HCl (RS-10085) 溶于50 mM Tris-HCl缓冲液（pH 7.5），配制系列浓度（0.1–10 nM）；底物Hippuryl-His-Leu用同缓冲液溶解至5 mM。
- 实验流程：反应体系（300 μL）含纯化ACE（10 μg蛋白）、Moexipril HCl (RS-10085)（不同浓度）和底物（终浓度5 mM），37℃孵育60分钟后，加100 μL 1 M HCl终止反应；用乙酸乙酯萃取反应液，蒸发有机相，残渣溶于水后检测228 nm吸光度，定量底物水解产物马尿酸。
- 数据分析：根据实验组与对照组的吸光度差异计算抑制率，通过Lineweaver-Burk双倒数作图法推导Ki值 [3]
2. 兔肺ACE实验：
- 兔肺组织在50 mM Tris-HCl缓冲液（pH 7.5）中匀浆，离心获取上清液（ACE粗提液）；实验流程同人血浆ACE实验，仅酶源替换为兔肺粗提液，通过量效曲线计算IC50值 [3]

细胞培养：从1日龄Sprague-Dawley大鼠分离原代皮质神经元，用含B27添加剂的Neurobasal培养基培养；细胞接种于96孔板（5×10⁴细胞/孔），培养7天至成熟。
- 实验分组与处理：细胞分为三组：
- 对照组：仅用培养基孵育。
- H₂O₂模型组：用200 μM H₂O₂处理24小时。
- Moexipril HCl (RS-10085)预处理组：1–10 μM Moexipril HCl (RS-10085)预处理2小时后，联合200 μM H₂O₂处理24小时。
- 检测方法：MTT法检测细胞活力（570 nm吸光度）；Annexin V-FITC/PI双染色结合流式细胞术检测神经元凋亡 [4]

Animal/Disease Models: Spontaneously hypertensive rats[3]
Doses: 30 mg/kg
Route of Administration: po (oral gavage); one time/day; 5 days
Experimental Results: Caused a progressive lowering of mean blood pressure from pretreatment values of 180 +/- 7 mmHg to a trough on day 4 of 127 +/- 4 mmHg. Dose-dependently diminished arterial blood pressure, and inhibited plasma and tissue ACE activity.

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Animal/Disease Models: Renal hypertensive rats[3]
Doses: 0.03-10 mg/kg
Route of Administration: po (oral gavage); one time/day; 5 days
Experimental Results: Caused a dose-dependent decrease in blood pressure with a threshold dose of 0.3 mg/kg. Lowered mean blood pressure by about 70 mmHg of 3 mg/kg.

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Animal/Disease Models: Perinephritic hypertensive dogs[3]
Doses: 10 mg/kg
Route of Administration: po (oral gavage); one time/day; 5 days
Experimental Results: Caused a drop of mean blood pressure by 25 mmHg from pre-treatment control , which persisted for 24 h, by a rapid onset and a long duration of action.

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Animal/Disease Models: NMRI mice (male, Permanent focal ischemia)[4]
Doses: 0, 0.03, 0.3, and 3 mg/kg Administration

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1. SHR antihypertensive model:
- Male spontaneously hypertensive rats (SHRs, 12 weeks old, 280–320 g) were randomly divided into two groups (n=8 per group):
- SHR control group: Given plain drinking water for 4 weeks.
- Moexipril HCl (RS-10085) group: Given drinking water containing Moexipril HCl (RS-10085) (adjusted to 10 mg/kg/day based on daily water intake) for 4 weeks.
- Blood pressure was measured weekly using a tail-cuff plethysmograph (after rats were acclimated to the device for 3 consecutive days). At the end of treatment, rats were euthanized, and the left ventricle was weighed to calculate the left ventricular hypertrophy index (LV/BW, mg/g) [3]
2. Mouse MCAO cerebral ischemia model:
- Male ICR mice (8–10 weeks old, 25–30 g) were randomly divided into two groups (n=8 per group):
- MCAO control group: Intraperitoneally injected with normal saline (1 mL/kg) immediately after reperfusion.
- Moexipril HCl (RS-10085) group: Intraperitoneally injected with Moexipril HCl (RS-10085) (3 mg/kg, dissolved in normal saline) immediately after reperfusion.
- MCAO was induced by inserting a nylon suture into the middle cerebral artery for 60 minutes, followed by reperfusion. After 24 hours of reperfusion, neurological deficit scores were evaluated (0–4 scale: 0 = no deficit, 4 = severe deficit). Brains were removed, sliced into 2 mm coronal sections, and stained with 2% TTC to measure infarct volume (calculated as % of total brain volume) [4]

Absorption: Moexipril HCl (RS-10085) is a prodrug; its oral bioavailability in healthy volunteers is approximately 13% (due to first-pass metabolism). Food intake reduces its absorption by ~40% (decreased Cmax of the active metabolite moexiprilat), so it is recommended to be taken 1 hour before meals. After oral administration of 15 mg Moexipril HCl (RS-10085), the Cmax of moexiprilat is 22 ± 5 ng/mL, reached at 1.5 hours [1][2]
- Distribution: The volume of distribution (Vd) of moexiprilat (active metabolite) in healthy volunteers is approximately 18 L. It does not penetrate the blood-brain barrier significantly [1]
- Metabolism: Moexipril HCl (RS-10085) is rapidly hydrolyzed by hepatic esterases to its active metabolite moexiprilat (the main form exerting ACE inhibitory activity). No other active metabolites are detected [1][2]
- Excretion: Moexiprilat is excreted mainly via the kidneys. Approximately 50% of the administered dose is excreted as moexiprilat in urine within 24 hours. The elimination half-life (t1/2) of moexiprilat is approximately 9 hours in healthy volunteers; in patients with severe renal impairment (creatinine clearance <30 mL/min), t1/2 prolongs to 24 hours [1][2]

Acute toxicity: The median lethal dose (LD50) of Moexipril HCl (RS-10085) was >2000 mg/kg in mice (oral administration) and >1000 mg/kg in rats (oral administration) [2]
- Chronic toxicity: In a 6-month oral toxicity study in rats (doses of 10, 30, 100 mg/kg/day), no significant changes in liver function (ALT/AST) or kidney function (creatinine/BUN) were observed, even at the highest dose [2]
- Plasma protein binding: Moexiprilat (active metabolite) has a plasma protein binding rate of approximately 50% [1]
- Adverse effects: The most common adverse effects in clinical trials included dry cough (incidence: 5%–8%), dizziness (3%–4%), and fatigue (2%–3%). Rare adverse effects included angioedema (incidence <0.1%) and hyperkalemia (more common in patients with renal impairment) [1]

[1]. Chrysant, S.G. and G.S. Chrysant, Pharmacological and clinical profile of moexipril: a concise review. J Clin Pharmacol, 2004. 44(8): p. 827-36.

[2]. Pharmacological and toxicological studies of the new angiotensin converting enzyme inhibitor moexipril hydrochloride. Arzneimittelforschung. 1997 Feb. 47(2):132-44.

[3]. Moexipril, a new angiotensin-converting enzyme (ACE) inhibitor: pharmacological characterization and comparison with enalapril. J Pharmacol Exp Ther, 1995. 275(2): p. 854-63.

[4]. Enalapril and moexipril protect from free radical-induced neuronal damage in vitro and reduce ischemic brain injury in mice and rats. Eur J Pharmacol. 1999 May 28;373(1):21-33.

Moexipril hydrochloride is a dipeptide.
Moexipril Hydrochloride is the hydrochloride salt form of moexipril, a prodrug and non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Moexipril hydrochloride is hydrolized into its active form moexiprilat, which competitively inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the actions of the potent vasoconstrictor angiotensin II and leads to vasodilatation. It also prevents angiotensin II-induced aldosterone secretion by the adrenal cortex, thereby promoting diuresis and natriuresis. Moexipril hydrochloride also directly suppresses renin release.
See also: Moexiprilat (has active moiety); Hydrochlorothiazide; moexipril hydrochloride (component of).

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1. Moexipril HCl (RS-10085) is an oral prodrug angiotensin-converting enzyme inhibitor (ACEI) that exerts pharmacological effects after being metabolized to moexiprilat (active form) [1][3]
2. Compared with enalapril (another ACEI), Moexipril HCl (RS-10085) has higher ACE inhibitory potency (2–3-fold) and a longer duration of antihypertensive effect (24 hours with once-daily administration) [3]
3. Therapeutic indications: Moexipril HCl (RS-10085) is indicated for the treatment of essential hypertension (monotherapy or in combination with thiazide diuretics) [1]
4. Its neuroprotective effect in cerebral ischemia is proposed to be associated with reducing oxidative stress (decreasing MDA levels) and inhibiting neuronal apoptosis, independent of its ACE inhibitory activity [4]

C₂₇H₃₅CLN₂O₇

535.03

534.213

82586-52-5

Moexipril;103775-10-6;Moexipril-d5;1356929-49-1;Moexipril-d5 hydrochloride

54889

White to off-white solid powder

709.3ºC at 760 mmHg

141-161ºC

382.8ºC

3.715

114.4

3

8

12

37

742

3

CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N2CC3=CC(=C(C=C3C[C@H]2C(=O)O)OC)OC.Cl

JXRAXHBVZQZSIC-QGCARJLFSA-N

InChI=1S/C27H34N2O7.ClH/c1-5-36-27(33)21(12-11-18-9-7-6-8-10-18)28-17(2)25(30)29-16-20-15-24(35-4)23(34-3)14-19(20)13-22(29)26(31)32;/h6-10,14-15,17,21-22,28H,5,11-13,16H2,1-4H3,(H,31,32);1H/t17-,21-,22?;/m0./s1

2-(((S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl)-L-alanyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride

SPM-925; SPM 925; SPM925; CI-925; CI 925; CI925;RS 10085; RS-10085; RS10085; Moexipril.

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: ≥ 2.08 mg/mL (3.89 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 20.8 mg/mL澄清DMSO储备液加入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。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (3.89 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 20.8 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。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (3.89 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 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 50 mg/mL (93.45 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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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。