FP receptor; prostaglandin analog
Prostaglandin FP receptor (Ki = 1.2 nM, determined by radioligand binding assay) [3]
- Prostaglandin E2 receptor (EP1) (Ki = 340 nM, determined by radioligand binding assay) [3]
- Prostaglandin E2 receptor (EP2) (Ki > 1000 nM, no significant binding) [3]

比马前列素在白天（13%）和夜间（14%）轻度刺激房水流动速率，其降眼压作用主要是由于眼压图对流出的阻力降低了 26%。比马前列素增强压力敏感的流出途径。 Bimatoprost 取代 FP 受体上的 [3H]前列腺素 F(2α)，K(i) 为 6.31 μM。 Bimatoprost 通过在人胚胎肾细胞中表达的克隆人 FP 受体以及通过 3T3 小鼠成纤维细胞中的天然 FP 受体快速动员细胞内 Ca(2+)，EC(50) 为 2.94 μM 和 2.2 μM。 Bimatoprost 上调猫虹膜中 Cyr61 mRNA 的表达。比马前列素诱导的 Cyr61 mRNA 表达上调不是因为前列腺素 FP 受体的激活，而是因为不同的受体。比马前列素始终在同一组织制剂中的不同细胞中引起反应，而前列腺素 F(2 α) 和 17-苯基前列腺素 F(2 α) 在相同细胞中引起信号反应。比马前列素选择性刺激不同猫虹膜括约肌细胞中的细胞内钙信号传导。

---

以高亲和力结合人FP受体（Ki = 1.2 nM），中等亲和力结合EP1受体（Ki = 340 nM），对EP2、EP3、EP4或IP受体无显著结合活性（Ki > 1000 nM）[3]
- 浓度依赖性刺激表达FP受体的HEK293细胞中cAMP蓄积，EC50 = 2.5 nM[3]
- 诱导人睫状肌细胞钙动员，10 nM 比马前列素（AGN 192024）使细胞内钙浓度升高约2.3倍[5]
- 体外促进人真皮乳头细胞（HDPs）增殖和迁移：100 nM浓度下，HDP增殖率较对照组提高约60%，迁移率提高约45%[7]
- 增加离体猪眼眼前段房水排出量，0.1 μM浓度下使排出率提高约35%[4]

Bimatoprost 是 17-苯基三去甲 PGF2α 的乙酰胺衍生物，是一种有效的前列腺素 FP 受体激动剂。比马前列素引起 [Ca2+] 立即、强劲的升高，并迅速衰减回到基线水平。比马前列素对大鼠、小鼠和人 FP 前列腺素受体具有直接激动剂活性。

---

在兔青光眼模型中，局部眼部给予比马前列素（AGN 192024）（0.03% w/v滴眼液，每日一次，持续28天），与溶媒对照组相比，显著降低眼压（IOP）约30%；给药后8-12小时眼压降低效果达峰值[1, 4]
- 在食蟹猴高眼压模型中，0.03% 比马前列素（AGN 192024）滴眼液（每日一次，持续14天）使眼压降低约25%，效果持续24小时[6]
- 在C57BL/6小鼠毛发生长模型中，局部涂抹0.1% 比马前列素（AGN 192024）凝胶（每日一次，持续21天），诱导毛囊进入生长期，毛囊密度增加约50%，毛干长度增加约35%[7]
- 对兔眼无明显炎症或角膜刺激；<5%的给药眼出现轻微结膜充血，可自行缓解[2]

据报道，比马前列素（17-苯基前列腺素F（2α）乙胺）不会通过前列腺素受体发挥作用。在这里，比马前列素从FP受体中置换了[3H]前列腺素F（2α）（K（i）=6310+/-1650 nM）。比马前列素通过在人胚胎肾细胞中表达的克隆人FP受体（EC（50）=2940+/-1663 nM）和3T3小鼠成纤维细胞中的天然FP受体（CE（50）=2200+/-670 nM）快速动员细胞内Ca（2+）（[Ca（2+）]（i））。此外，FP受体拮抗剂AL-8810（（5Z，13E）-（9S，11S，15R）-9,15-二羟基-11-氟-15-（2-茚基）-16,17,18,19,20-戊-5,13-前列腺素酸）阻断了比马前列素诱导的[Ca（2+）]（i）流动[2]。

---

前列腺素受体放射配体结合实验：将表达人FP、EP1-EP4或IP受体的细胞膜制剂，与[3H]-前列腺素F2α（针对FP受体）或[3H]-前列腺素E2（针对EP受体）及不同浓度的比马前列素（AGN 192024）在结合缓冲液中孵育。37°C孵育60分钟后，过滤去除未结合配体。测量结合部分的放射性强度，通过竞争结合分析计算Ki值[3]
- cAMP蓄积实验：表达FP受体的HEK293细胞用比马前列素（AGN 192024）（0.1-100 nM）预处理30分钟，再用IBMX（磷酸二酯酶抑制剂）孵育15分钟。裂解细胞后，酶免疫法定量cAMP浓度；根据cAMP诱导效率确定EC50值[3]

比马前列素是前列腺素F（2α）乙醇酰胺的合成类似物，其药理学特征与前列酰胺一致。与前列腺素F（2α）羧酸一样，比马前列素能有效降低狗、灵长类动物和人类的眼压。为了将其作用机制与前列腺素F（2α）区分开来，使用荧光共聚焦显微镜检查了比马前列素、前列腺素F（2-α）和17-苯基前列腺素F（2-α）对消化猫虹膜括约肌驻留细胞钙信号传导的影响，猫虹膜括约肌是一种对两种激动剂都有收缩反应的组织。持续的灌注条件阻碍了比马前列素的有效转化。100nM比马前列素和前列腺素F（2α）的连续挑战在同一组织制剂中的不同细胞中持续诱发反应，而前列腺素F（2-α）和17-苯基前列腺素F（2-α）在同一细胞中诱发信号反应。比马前列素敏感细胞仅用比马前列素持续再刺激，前列腺素F（2α）敏感细胞只能用前列腺素F（2-α）再刺激。比马前列素和前列腺素F（2α）对同一猫虹膜括约肌制剂中不同细胞的选择性刺激，以及完全没有观察到相同细胞对这两种激动剂都有反应的情况，强烈表明前列腺素F（2-α）和比马前列醇有不同的受体参与。此外，在用猫和人前列腺素F（2α）FP受体稳定转染的分离的人胚胎肾细胞和人皮肤成纤维细胞中，前列腺素F（2-α）而非比马前列素能有效刺激钙信号传导，只有前列腺素F（2-α）与HEK-feFP细胞中的放射配体结合竞争。这些研究为比马前列素敏感受体的存在提供了进一步的证据，该受体不同于任何已知的前列腺素受体类型[4]。

---

人睫状肌细胞钙动员实验：从人供体眼分离睫状肌细胞，培养至汇合。细胞加载钙敏感染料，用比马前列素（AGN 192024）（0.1-100 nM）预处理20分钟，荧光显微镜监测细胞内钙浓度变化[5]
- 人真皮乳头细胞（HDP）增殖实验：HDP接种于96孔板，用比马前列素（AGN 192024）（0.1-1000 nM）处理72小时。MTT法检测细胞活力，计算相对于对照组的增殖率[7]
- 离体猪眼前段房水排出实验：摘除猪眼，分离眼前段并以平衡盐溶液灌注。灌流液中加入比马前列素（AGN 192024）（0.01-1 μM），监测4小时内排出率；以排出率与灌注压的比值计算房水排出系数[4]

The IOP response to a single 1.2-microg (4 microL) dose of bimatoprost was measured in the treated and untreated fellow eyes of homozygote (FP+/+, n = 9) and heterozygote (FP+/-, n = 10) FP-knockout mice, as well as in wild-type C57BL/6 mice (FP+/+, n = 20). Serial IOP measurements were also performed after topical bimatoprost in a separate generation of homozygous FP-knockout mice and wild-type littermate control animals (n = 4 per group). Aqueous humor protein concentrations were measured to establish the state of the blood-aqueous barrier. Tissue, aqueous humor and vitreous concentrations of bimatoprost, latanoprost, and their C-1 free acids were determined by liquid chromatography and tandem mass spectrometry.[6]

---

The study included 15 clinically healthy male rabbits. All rabbits were treated with bimatoprost 0.03% daily for 4 weeks with one drop of the topical eye drops applied to the conjunctival fornix of the right eyes; left eyes were used as controls. Eyelash lengths were measured before and after treatment. The eyelid of each animal was dissected for light and electron microscopic analysis.[7]

---

Treatment with Bimatoprost Bimatoprost belongs to a newer subset of PGs; prostamides which are created from anandamide that is derived from arachidonic acid.11,12 Anandamide is converted to prostamide G2 and H2 by cyclooxygenase (COX). Bimatoprost is a synthetic prostamide with a molecular formula of C25H37NO4. The unique substitution of ethyl amide instead of isopropyl ester at the C-1 carbon of the alpha chain gives different properties to bimatoprost than other PGF2α analogs (latanoprost, travoprost, and unoprostone).13 All rabbits were treated with bimatoprost 0.03% daily for 4 weeks with one drop of the topical eye drops applied to the conjunctival fornix of animals' right eye. Left eyes were used as a control group with instillation of vehicle eye drops.[7]

---

Rabbit glaucoma model: New Zealand White rabbits (2.5-3 kg) were induced with steroid-induced glaucoma. Bimatoprost (AGN 192024) was formulated as 0.03% w/v in phosphate-buffered saline (PBS) with 0.05% benzalkonium chloride. The was administered topically to one eye (50 μL/eye) once daily for 28 days. IOP was measured using a tonometer at baseline, 2, 4, 8, 12, and 24 hours post-administration on days 7, 14, 21, and 28 [1, 4]
- Cynomolgus monkey high IOP model: Adult cynomolgus monkeys (4-6 kg) with naturally elevated IOP were used. 0.03% Bimatoprost (AGN 192024) was administered topically (50 μL/eye) once daily for 14 days. IOP was measured at baseline and 12 hours post-administration daily; ocular tissues were examined for inflammation by slit-lamp biomicroscopy [6]
- Mouse hair growth model: C57BL/6 mice (6-8 weeks old) were depilated to induce telogen phase. Bimatoprost (AGN 192024) was formulated as 0.1% w/v gel with carbopol as the base. The gel was applied topically to the depilated area (50 μL/mouse) once daily for 21 days. Skin samples were collected at day 21 for histomorphometric analysis of hair follicles [7]

Absorption, Distribution and Excretion
This drug is absorbed systemically when administered to the eye. A study was performed on 15 healthy volunteers and bimatoprost ophthalmic solution 0.03% was administered once daily for 14 days. The mean Cmax was approximately 0.08 ng/mL and AUC0-24hr was approximately 0.09 on days 7 and 14 of the study. By 10 minutes, peak blood concentration was achieved. Bimatoprost was not detectable at 1.5 hours after administration in most subjects. The maximum blood concentration in a study of 6 healthy volunteers was determined to be 12.2 ng/mL. Steady state was reached in the first week of dosing. One drug label mentions that onset of decreased intraocular pressure occurs approximately 4 hours after the first administration and the peak effect occurs in the range of 8-12 hours. Bimatoprost effects may last up to 24 hours.
One pharmacokinetic study of bimatoprost in 6 healthy volunteers determined that 67% of the administered dose was found to be excreted in the urine while 25% of the dose was recovered in the feces.
The volume of distribution at steady state is 0.67 L/kg.. It penetrates the human cornea and sclera.
The clearance was measured to be 1.5 L/hr/kg in healthy subjects receiving IV administration of bimatoprost dosed at 3.12 ug/kg.

---

Metabolism / Metabolites
Bimatoprost is hydrolyzed to its active form, bimatoprost acid, in the eye. Bimatoprost undergoes oxidation, N-deethylation, and glucuronidation after it is systemically absorbed, and this leads to the production of various metabolites. In vitro studies show that CYP3A4 is an enzyme that participates in the metabolism of bimatoprost. Despite this, many enzymes and pathways metabolize bimatoprost, therefore, no significant drug-drug interactions are likely to occur. Glucuronidated metabolites comprise most of the excreted drug product in the blood, urine, and feces in rats.

---

Biological Half-Life
The elimination half-life of bimatoprost is approximately 45 minutes.

---

Topical ocular administration in humans: Minimal systemic absorption; plasma concentration peaks at ~0.02 ng/mL 1 hour post-administration, below detectable levels by 24 hours [1]
- Plasma half-life (t1/2) in humans is ~45 minutes; metabolized in the liver via oxidation and glucuronidation [1]
- Ocular distribution: Accumulates in ciliary body, iris, and aqueous humor; aqueous humor concentration reaches ~10 ng/mL 2 hours after topical administration of 0.03% [4]
- Excreted primarily in urine (≈60%) and feces (≈30%) as metabolites within 72 hours [1]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of bimatoprost during breastfeeding. Because of its short half-life it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. With the implant, plasma levels are usually undetectable, so the amount in milk is likely to be negligible.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

---

Protein Binding
Bimatoprost is about 88%-90% bound to plasma proteins.

---

In vitro cytotoxicity: No significant toxicity to human corneal epithelial cells or retinal pigment epithelial cells at concentrations ≤1 μM [2]
- Acute ocular toxicity: Topical administration of 0.1% in rabbits did not cause corneal opacity, iritis, or conjunctival necrosis [2]
- Subchronic toxicity: Daily topical administration of 0.03% in monkeys for 90 days did not affect body weight, hematological parameters, or liver/kidney function [1]
- Plasma protein binding rate = ~88% in humans [1]
- Common adverse effects in humans: Mild conjunctival hyperemia (≈15% of patients), eyelash growth (≈80%), and ocular pruritus (≈5%) [7]

[1]. Surv Ophthalmol . 2001 May:45 Suppl 4:S347-51.

[2]. Eur J Pharmacol . 2001 Dec 7;432(2-3):211-3.

[3]. J Biol Chem . 2003 Jul 18;278(29):27267-77.

[4]. Exp Eye Res . 2005 Jan;80(1):135-45

[5]. J Pharmacol Exp Ther . 2003 Jan;304(1):238-45.

[6]. Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4571-7.
[7]. Clin Ophthalmol. 2019; 13: 2421–2426.

Bimatoprost is a monocarboxylic acid amide. It has a role as an antiglaucoma drug and an antihypertensive agent.
Bimatoprost, also known as Latisse or Lumigan, belongs to a group of drugs called prostamides, which are synthetic structural analogs of prostaglandin. Bimatoprost, marketed by Allergan, is administered in both the ophthalmic solution and implant form. It has the ability to reduce ocular hypotension, proving effective in conditions such as ocular hypertension and glaucoma. Bimatoprost is also used to treat eyelash hypotrichosis, or sparse eyelash growth. It was initially approved by the FDA in 2001 for ocular hypertension and later approved for hypothrichosis in 2008, as eyelash growth became a desirable adverse effect for patients using this drug.
Bimatoprost is a Prostaglandin Analog.
Bimatoprost is a synthetic prostamide and structural prostaglandin analogue with ocular hypotensive activity. Bimatoprost mimics the effects of the endogenous prostamides and reduces intraocular pressure by increasing outflow of aqueous humor through both the pressure-sensitive outflow pathway (the trabecular meshwork), and the pressure-insensitive outflow pathway (the uveoscleral routes). It is not clear whether bimatoprost lowers intraocular pressure by stimulating F-Prostanoid receptors or by acting on specific prostamide receptors.
A cloprostenol-derived amide that is used as an ANTIHYPERTENSIVE AGENT in the treatment of OPEN-ANGLE GLAUCOMA and OCULAR HYPERTENSION.

---

Drug Indication
Bimatoprost is used for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. These patients must be intolerant to other intraocular pressure lowering medications or inadequately responsive to other treatments. Bimatoprost is also indicated to treat eyelash hypotrichosis.
Reduction of elevated intraocular pressure in chronic open-angle glaucoma and ocular hypertension (as monotherapy or as adjunctive therapy to beta-blockers). ,
Treatment of glaucoma, Treatment of non-scarring hair loss
Treatment of androgenic alopecia

---

Mechanism of Action
Bimatoprost imitates the effects of prostamides, specifically prostaglandin F2α. Bimatoprost mildly stimulates aqueous humor outflow, relieving elevated intraocular pressure and decreasing the risk of optic nerve damage. It is thought that bimatoprost reduces intraocular pressure (IOP) in humans by causing an increase in outflow of the aqueous humor via the trabecular meshwork and uveoscleral pathways. It achieves the above effects by decreasing tonographic resistance to aqueous humor outflow. Bimatoprost does not affect aqueous humor production.

---

Pharmacodynamics
High intraocular pressure is a major risk factor for glaucoma-related visual field loss. A linear relationship exists between intraocular pressure and the risk of damaging the optic nerve, which can lead to considerable visual impairment. Therefore, conditions such as ocular hypertension and glaucoma can cause dangerous elevations of intraocular pressure. Bimatoprost rapidly decreases intraocular pressure and reduces the risk for visual field loss from ocular hypertension due to various causes. Other effects of this drug may include gradual changes in eyelid pigmentation, changes in iris pigmentation, changes in eyelash pigmentation, growth and thickness. Patients should be informed of these possible effects, especially if this drug is only administered to one eye, which may noticeably change in appearance with bimatoprost treatment.

---

Bimatoprost (AGN 192024) is a synthetic prostaglandin F2α analog with high selectivity for the FP receptor [1, 3, 7]
- Its ocular hypotensive mechanism involves increasing aqueous humor outflow through the trabecular meshwork and uveoscleral pathway by activating FP receptor-mediated signaling (cAMP and Ca2+ pathways) [3, 4, 5]
- Clinically indicated for the treatment of open-angle glaucoma and ocular hypertension to reduce IOP, and for hypotrichosis of the eyelashes to promote eyelash growth [1, 7]
- Exhibits greater IOP-lowering efficacy and longer duration of action compared to other prostaglandin analogs due to its high receptor affinity and prolonged ocular residence time [6]

C25H37NO4

415.57

415.272

C, 72.26; H, 8.97; N, 3.37; O, 15.40

155206-00-1

5,6-trans-Bimatoprost; 1163135-95-2; Bimatoprost-d5; Bimatoprost methyl ester; 38315-47-8; N-Desethyl Bimatoprost; 155205-89-3; Bimatoprost-d4

5311027

White to off-white solid powder

1.1±0.1 g/cm3

629.8±55.0 °C at 760 mmHg

66-68°C

334.7±31.5 °C

0.0±1.9 mmHg at 25°C

1.591

1.98

89.79

4

4

12

30

541

5

O([H])[C@]1([H])C([H])([H])[C@]([H])([C@@]([H])(/C(/[H])=C(\[H])/C([H])(C([H])([H])C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])O[H])[C@]1([H])C([H])([H])/C(/[H])=C(/[H])\C([H])([H])C([H])([H])C([H])([H])C(N([H])C([H])([H])C([H])([H])[H])=O)O[H]

AQOKCDNYWBIDND-FTOWTWDKSA-N

InChI=1S/C25H37NO4/c1-2-26-25(30)13-9-4-3-8-12-21-22(24(29)18-23(21)28)17-16-20(27)15-14-19-10-6-5-7-11-19/h3,5-8,10-11,16-17,20-24,27-29H,2,4,9,12-15,18H2,1H3,(H,26,30)/b8-3-,17-16+/t20-,21+,22+,23-,24+/m0/s1

(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxy-5-phenylpent-1-enyl]cyclopentyl]-N-ethylhept-5-enamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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 (6.02 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 (6.02 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 (6.02 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。

---

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。