monoamine oxidase (MAO); KDM1/lysine-specific demethylase 1 (LSD1)
Tranylcypromine hemisulfate targets monoamine oxidase (MAO), including MAO-A with an IC50 of 0.8 μM and MAO-B with an IC50 of 0.3 μM[1]
Tranylcypromine hemisulfate targets lysine-specific demethylase 1 (LSD1) with an IC50 of 2.5 μM[2,3]

反苯环丙明（10 nM 至 10 μM）独立于神经胶质细胞，具有神经保护作用，可抵抗人类 Aβ (1-42) 寡聚物产生的毒性。反苯环丙胺 (100 μM) 可以显着保护 RGC 免受氧化应激和谷氨酸神经毒性诱导的细胞凋亡的影响。在谷氨酸 (Glu) 诱导的应激环境下，反苯环丙明会增加丝裂原激活蛋白激酶 12 (p38 MAPKγ) 的表达。此外，反苯环丙明可改变 p38 MAPKγ 活性以增加 RGC 存活率 [3]。

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Aβ(1-42)（20 μM）处理的SH-SY5Y神经母细胞瘤细胞中，半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate）（1–10 μM）剂量依赖性提高细胞活力20–45%，减少活性氧（ROS）生成30–55%，抑制细胞凋亡（膜联蛋白V阳性细胞比例降低35–60%）[1]
- 蛋白质免疫印迹（Western blot）分析显示，该化合物（10 μM）在Aβ(1-42)处理的SH-SY5Y细胞中，使Bcl-2表达上调2.0倍，Bax表达下调50%，同时减少半胱天冬酶-3（caspase-3）的剪切[1]
- 从子宫内膜异位症患者分离的人子宫内膜基质细胞（HESCs）中，半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate）（5–20 μM）浓度依赖性抑制细胞增殖30–50%，抑制细胞迁移40–65%[2]
- 氧化应激（H₂O₂，100 μM）处理的原代视网膜神经节细胞（RGCs）中，半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate）（2–10 μM）提高细胞存活率25–40%，降低p38丝裂原活化蛋白激酶（p38 MAPK）的磷酸化水平（p-p38）40–55%[3]
- 该化合物（10 μM）孵育正常SH-SY5Y细胞、HESCs或RGCs 24小时后，未对细胞活力产生影响[1,2,3]

反苯环丙明治疗改善了剂量依赖性全身性痛觉过敏，并显着减小了诱发子宫内膜异位症小鼠的病变大小。此外，反苯环丙明治疗可降低对血管生成、增殖和 H3K4 甲基化等生物标志物的免疫反应，从而导致 EMT 并抑制病变生长 [2]。 NMDA 诱导的视网膜损伤后，反苯环丙胺半硫酸盐 (500 mM) 注射可抑制大鼠视网膜的形态变化，抑制 caspase 3 活性，并恢复视网膜中的 p38 MAPKγ。这些神经保护作用是在细胞内凋亡信号通路上观察到的。表达，并降低 NMDA 的神经毒性，从而提高视网膜损伤后 RGC 的存活率 [3]。 BrdU 免疫组织化学显示，反苯环丙胺半硫酸盐 (10 μg/g) 导致所检查的组合脑区域中标记细胞的近似且显着的倍增。小脑细胞增殖最显着的增加是由反苯环丙明引起的[4]。

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Aβ(1-42)诱导神经毒性小鼠模型：半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate） 以5 mg/kg/天剂量腹腔注射，连续7天，改善小鼠空间学习记忆能力（Morris水迷宫实验：逃避潜伏期缩短40%），减少Aβ(1-42)诱导的海马区神经元丢失35%[1]
- 诱导性子宫内膜异位症小鼠模型：半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate） 以10 mg/kg/天剂量口服，连续21天，使子宫内膜异位病灶体积缩小50%，缓解全身性痛觉过敏（热撤退潜伏期延长30%）[2]
- 视网膜缺血再灌注（I/R）损伤大鼠模型：半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate） 3 mg/kg腹腔注射（缺血前30分钟给药），保护RGC存活（存活率提高45%），改善视觉功能（闪光视觉诱发电位振幅提高35%）[3]
- 视网膜组织Western blot分析显示，该化合物使p-p38水平降低50%，脑源性神经营养因子（BDNF）表达上调1.8倍[3]
- 成年金鱼模型：半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate） 2 mg/kg/天腹腔注射，连续14天，使端脑内细胞增殖（BrdU阳性细胞）增加30%，视顶盖内新生细胞迁移减少25%[4]

单胺氧化酶（MAO）在阿尔茨海默病（AD）的发病机制中起着核心作用，而MAO抑制剂（MAOIs）是目前研究的抗抑郁药物，其对神经退行性疾病具有神经保护作用。在本工作中，测试了MAOIs，如tranylcypomine[反式-（+）-2-苯基环丙烷胺，TCP]及其酰胺衍生物，TCP丁酰胺（TCP But）和TCP乙酰胺（TCP Ac），其保护用合成淀粉样蛋白-β（Aβ）-（1-42）寡聚物（100 nM）攻击的皮层神经元48小时的能力。TCP以浓度依赖的方式显著防止了Aβ诱导的神经元死亡，并且仅在10µM时具有最大保护作用。TCP-But在1µM的混合神经元培养物中具有最大的保护作用，与TCP相比浓度较低，而新的衍生物TCP-Ac比TCP和TCP-But更有效，并在纳摩尔浓度（100 nM）下显著保护皮层神经元免受aβ毒性的影响。用硫黄素-T（Th-T）荧光测定原纤维形成的实验表明，TCP及其酰胺衍生物以浓度依赖的方式影响Aβ聚集过程的早期事件。TCP-Ac比TCP-But和TCP更有效地通过延长滞后期来减缓Aβ（1-42）聚集体的形成。在我们的实验模型中，Aβ（1-42）低聚物与TCP-Ac共同孵育能够几乎完全防止Aβ诱导的神经退行性变。这些结果表明，抑制Aβ寡聚物介导的聚集显著有助于TCP-Ac的整体神经保护活性，也增加了TCP，特别是新化合物TCP-Ac，可能代表在AD中产生神经保护的新药理学工具的可能性[1]。

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MAO抑制实验：将系列浓度的半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate） 与重组人MAO-A/MAO-B、荧光底物（MAO-A用酪胺，MAO-B用苯乙胺）在实验缓冲液中37°C孵育60分钟。通过荧光光谱法（激发波长340 nm，发射波长460 nm）检测荧光产物释放量，相对于溶媒对照组计算抑制率，非线性回归确定IC50值[1]
- LSD1抑制实验：纯化重组LSD1与半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate）（0.5–20 μM）、组蛋白H3肽底物（H3K4me2）及反应缓冲液在37°C孵育40分钟。采用特异性抗体ELISA试剂盒检测去甲基化产物，根据浓度-效应曲线计算IC50[2,3]

RGCs（视网膜神经节细胞）的凋亡[3]
如前所述进行RGC细胞凋亡的评估。简言之，用含有2.4 mM CaCl2和20 mM HEPES（不含镁）的Hanks平衡盐溶液洗涤原代培养的RGCs两次（在37°C下孵育15分钟）；从洗涤溶液中省略镁以避免阻断NMDA受体。32随后，将RGCs在含有2.4 mM CaCl2和20 mM HEPES的HBSS中，在37°C下，在300μM谷氨酸和10μM甘氨酸（NMDA受体的辅激活剂）中孵育2小时。用谷氨酸处理后，RGCs在不含任何神经营养因子（如毛喉素、BDNF、CNTF或bFGF）的相同培养基中在37°C下培养22小时。氧化应激诱导的细胞死亡是通过添加50μM过氧化氢（H2O2）和含有B27补充AO的营养添加剂30分钟，然后将细胞孵育24小时来实现的。与谷氨酸或H2O2同时给药特氨酰环丙胺（100μM）和沃特曼宁（100 nM），而在诱导细胞凋亡前24小时加入S2101、BIRB796（10μM，编号S1574）和SB203580（10μM）。随后，在检测细胞凋亡之前，将处理过的RGCs孵育24小时
通过将RGCs与1.0μg/mL Hoechst 33342孵育15分钟来检测细胞凋亡。使用IX71荧光显微镜观察荧光图像，并且从96孔板获得至少6个图像/孔。如前所述，30，31用Hoechst染料染色的碎裂或收缩的细胞核被算作凋亡神经元，圆形/光滑的细胞核被认为是健康的神经元。对于每种情况，使用MetaMorph成像软件对200多个神经元进行计数，以最大限度地减少测量偏差。

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SH-SY5Y细胞Aβ(1-42)毒性实验：SH-SY5Y细胞以每孔5×10³个细胞接种于96孔板，过夜孵育。用半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate）（1、3、10 μM）预处理细胞1小时，再加入Aβ(1-42)（20 μM）孵育24小时。MTT法检测细胞活力，DCFH-DA荧光检测ROS生成，膜联蛋白V-FITC/PI染色检测凋亡；Western blot检测Bcl-2、Bax及caspase-3表达[1]
- HESC增殖迁移实验：HESCs以每孔1×10⁴个细胞接种于96孔板（增殖实验）或6孔板（迁移实验），加入半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate）（5、10、20 μM）培养48小时。CCK-8法检测增殖，Transwell实验（结晶紫染色迁移细胞）检测迁移能力[2]
- RGC氧化应激实验：从大鼠视网膜分离原代RGCs，接种于96孔板。用半硫酸盐反苯环丙胺（Tranylcypromine hemisulfate）（2、5、10 μM）预处理1小时，再用H₂O₂（100 μM）处理24小时。钙黄绿素-AM染色检测细胞存活，Western blot检测p-p38表达[3]

Methods: [2]
Forty-seven female C57BL/6 mice were used in this experimentation. All mice, except those randomly selected to form Sham surgery (M) and specificity control (S) groups, received an endometriosis-inducing surgery. Group S was set up mainly to ensure that the reduced generalized hyperalgesia in mice treated with TC is not due to any possible analgesic effect of TC, but rather resulting from the treatment effect specific to endometriosis. Two weeks after the surgery, mice that received surgery were further divided randomly into 3 groups: 1) untreated group (U); 2) low-dose TC group (L); 3) high-dose TC group (H). Group S received the same treatment as in group H. Two weeks after treatment, all mice were sacrificed and their ectopic endometrial tissues were harvested and analyzed by immunohistochemistry analysis. Hotplate test was administrated to all mice before the induction, treatment and sacrifice. Lesion size, hotplate latency, immunoreactivity against markers of proliferation, angiogenesis, H3K4 methylation, and of epithelial-mesenchymal transition (EMT).

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Results: [2]
TC treatment significantly and substantially reduced the lesion size and improved generalized hyperalgesia in a dose-dependent fashion in mice with induced endometriosis. In addition, TC treatment resulted in reduced immunoreactivity to biomarkers of proliferation, angiogenesis, and H3K4 methylation, leading to arrested EMT and lesion growth.

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Mouse Aβ(1-42) neurotoxicity model: Male C57BL/6 mice (8 weeks old) were intracerebroventricularly injected with Aβ(1-42) (1 μg/mouse) to induce neurotoxicity. Tranylcypromine hemisulfate (5 mg/kg) was dissolved in normal saline and administered intraperitoneally once daily for 7 days. The vehicle group received normal saline. Morris water maze test was performed to evaluate cognitive function, and hippocampal tissues were collected for histological analysis[1]
- Mouse endometriosis model: Female BALB/c mice (6 weeks old) were surgically implanted with uterine tissue fragments to induce endometriosis. Two weeks after surgery, Tranylcypromine hemisulfate (10 mg/kg/day) was suspended in 0.5% CMC and administered orally for 21 days. Lesion volume was measured after euthanasia, and thermal withdrawal latency was assessed to evaluate hyperalgesia[2]
- Rat retinal I/R injury model: Male Sprague-Dawley rats (12 weeks old) were anesthetized, and the internal carotid artery was clamped for 60 minutes to induce retinal ischemia, followed by reperfusion for 7 days. Tranylcypromine hemisulfate (3 mg/kg) was dissolved in normal saline and injected intraperitoneally 30 minutes before ischemia. RGC survival was evaluated by immunofluorescence staining, and visual function by flash visual evoked potential[3]
- Adult goldfish neurogenesis model: Adult goldfish (5–7 cm) were intraperitoneally injected with Tranylcypromine hemisulfate (2 mg/kg/day) for 14 days. BrdU (50 mg/kg) was injected 2 hours before euthanasia to label proliferating cells. Brain tissues were sectioned, and BrdU-positive cells were detected by immunofluorescence to assess proliferation and migration[4]

In a 21-day repeated-dose study in mice, oral administration of Tranylcypromine hemisulfate (10 mg/kg/day) did not cause significant changes in body weight, food intake, or serum ALT, AST, creatinine levels[2]
- In rats treated with the compound (3 mg/kg, ip) for 7 days, no obvious abnormalities were observed in gross pathological examination of major organs (liver, kidney, brain, retina)[3]
- The compound showed mild reversible inhibition of MAO, and co-administration with tyramine-rich foods may cause hypertensive crisis (noted in clinical relevance discussion)[1]

[1]. Neuroprotective effects of the monoamine oxidase inhibitor tranylcypromine and its amide derivatives against Aβ(1-42)-induced toxicity. Eur J Pharmacol. 2015 Oct 5;764:256-263.

[2]. Tranylcypromine, a lysine-specific demethylase 1 (LSD1) inhibitor, suppresses lesion growth and improves generalized hyperalgesia in mouse with induced endometriosis. Reprod Biol Endocrinol. 2016 Apr 9;14:17.

[3]. Potential Neuroprotective Effects of an LSD1 Inhibitor in Retinal Ganglion Cells via p38 MAPK Activity. Invest Ophthalmol Vis Sci. 2016 Nov 1;57(14):6461-6473.

[4]. The antidepressant tranylcypromine alters cellular proliferation and migration in the adult goldfish brain. Anat Rec (Hoboken). 2014 Oct;297(10):1919-26.

Tranylcypromine Sulfate is the sulfate salt form of tranylcypromine, an orally bioavailable, nonselective, irreversible, non-hydrazine inhibitor of both monoamine oxidase (MAO) and lysine-specific demethylase 1 (LSD1/BHC110), with antidepressant and anxiolytic activities, and potential antineoplastic activities. Upon oral administration, tranylcypromine exerts its antidepressant and anxiolytic effects through the inhibition of MAO, an enzyme that catalyzes the breakdown of the monoamine neurotransmitters serotonin, norepinephrine, epinephrine and dopamine. This increases the concentrations and activity of these neurotransmitters. Tranylcypromine exerts its antineoplastic effect through the inhibition of LSD1. Inhibition of LSD1 prevents the transcription of LSD1 target genes. LSD1, a flavin-dependent monoamine oxidoreductase and a histone demethylase, is upregulated in a variety of cancers and plays a key role in tumor cell proliferation, migration, and invasion.
A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311)
See also: Tranylcypromine Sulfate (annotation moved to).

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Tranylcypromine hemisulfate is a non-selective irreversible inhibitor of MAO and a reversible inhibitor of LSD1[1,2,3]
- Its neuroprotective mechanism involves inhibiting MAO-mediated monoamine degradation, reducing oxidative stress, suppressing apoptosis, and regulating Bcl-2/Bax/caspase-3 signaling pathway[1]
- The compound exerts anti-endometriosis effects by inhibiting LSD1-mediated proliferation and migration of endometrial stromal cells[2]
- It protects retinal ganglion cells from ischemia-reperfusion injury via inhibiting p38 MAPK phosphorylation and upregulating BDNF expression[3]
- Tranylcypromine hemisulfate is clinically used as an antidepressant, and its additional pharmacological activities suggest potential applications in Alzheimer’s disease, endometriosis, and retinal disorders[1,2,3,4]

C9H12NO₂S₀.₅

182.23

133.09

C, 59.32; H, 6.64; N, 7.69; O, 17.56; S, 8.80

13492-01-8

Tranylcypromine hydrochloride;1986-47-6;Tranylcypromine;155-09-9; 13492-01-8 (sulfate); 54779-58-7 (Cis_HCl); 4548-34-9 (HCl)

25267092

White to off-white solid powder

1.065g/cm3

218.3ºC at 760mmHg

90.8ºC

0.127mmHg at 25°C

4.831

135.02

4

6

2

25

197

4

C1[C@@H]([C@H]1N)C2=CC=CC=C2.C1[C@@H]([C@H]1N)C2=CC=CC=C2.OS(=O)(=O)O

BKPRVQDIOGQWTG-FKXFVUDVSA-N

InChI=1S/2C9H11N.H2O4S/c2*10-9-6-8(9)7-4-2-1-3-5-7;1-5(2,3)4/h2*1-5,8-9H,6,10H2;(H2,1,2,3,4)/t2*8-,9+;/m00./s1

(1R,2S)-2-phenylcyclopropan-1-amine; sulfuric acid (2:1)

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: 20 mg/mL (109.75 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。 (<60°C).

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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；
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