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: Moxipril hydrochloride (RS-10085) is a prodrug; its bioavailability in healthy volunteers is approximately 13% after oral administration (due to first-pass metabolism). Food intake reduces its absorption by approximately 40% (reducing the Cmax of the active metabolite moxipril), therefore it is recommended to take it 1 hour before meals. After oral administration of 15 mg moxipril hydrochloride (RS-10085), the peak plasma concentration (Cmax) of moxipril was 22 ± 5 ng/mL, reached in 1.5 hours [1][2]. Distribution: The volume of distribution (Vd) of moxipril (the active metabolite) in healthy volunteers is approximately 18 L. It does not cross the blood-brain barrier significantly [1]. Metabolism: Moxipril hydrochloride (RS-10085) is rapidly hydrolyzed by hepatic esterases to the active metabolite moxipril (the major form that exerts ACE inhibitory activity). No other active metabolites were detected [1][2].
- Excretion: Moxiprilat is primarily excreted via the kidneys. Approximately 50% of the administered dose is excreted in the urine as moxiprilat within 24 hours. The elimination half-life (t1/2) of moxiprilat in healthy volunteers is approximately 9 hours; in patients with severe renal impairment (creatinine clearance <30 mL/min), t1/2 is prolonged to 24 hours [1][2]

Acute toxicity: The median lethal dose (LD50) of moxipril hydrochloride (RS-10085) in mice (oral) is >2000 mg/kg and in rats (oral) is >1000 mg/kg [2] - Chronic toxicity: In a 6-month oral toxicity study in rats (dose of 10, 30 and 100 mg/kg/day, respectively), no significant changes in liver function (ALT/AST) or kidney function (creatinine/BUN) were observed even at the highest dose [2] - Plasma protein binding: The plasma protein binding of moxipril (active metabolite) is approximately 50% [1] - Adverse reactions: The most common adverse reactions in clinical trials included dry cough (incidence: 5%–8%), dizziness (3%–4%) and fatigue (2%–3%). Rare adverse reactions include angioedema (incidence <0.1%) and hyperkalemia (more common in patients with renal insufficiency) [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. Moxipril hydrochloride is the hydrochloride form of moxipril, a prodrug and a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Moxipril hydrochloride is hydrolyzed to its active form, moxiprilat, which competitively inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the action of the potent vasoconstrictor angiotensin II, leading to vasodilation. It also prevents the adrenal cortex from secreting angiotensin II-induced aldosterone, thus promoting diuresis and sodium excretion. Moxipril hydrochloride can also directly inhibit renin release. See also: moxiprilat (containing the active fraction); hydrochlorothiazide; moxipril hydrochloride (ingredient). 1. Moxipril hydrochloride (RS-10085) is an oral prodrug of angiotensin-converting enzyme inhibitor (ACEI), which exerts its pharmacological effects after being metabolized to moxipril (the active form)[1][3]. 2. Compared with enalapril (another ACEI), moxipril hydrochloride (RS-10085) has higher ACE inhibitory efficacy (2-3 times) and a longer duration of antihypertensive effect (up to 24 hours after once-daily dosing)[3]. 3. Therapeutic indications: Moxipril hydrochloride (RS-10085) is indicated for the treatment of essential hypertension (as a monotherapy or in combination with thiazide diuretics)[1]. 4. Its neuroprotective effect on cerebral blood vessels is considered to be related to the reduction of oxidative stress (reducing MDA levels) and inhibition of neuronal apoptosis, but not to 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。