Compound 48/80 (hydrochloride)
(Synonyms: C48/80 trihydrochloride) 目录号 : GC43305Compound 48/80 (hydrochloride)是一种组胺 (histamine) 释放剂和肥大细胞 (mast cell) 脱颗粒剂，也是MrgprB2/X2（Mas-related G protein-coupled receptor B2/X2）的激动剂。Compound 48/80 (hydrochloride)能够抑制人血小板磷脂酰肌醇特异性磷脂酶 C (phosphatidylinositol-specific phospholipase C) 活性。
Cas No.:848035-21-2
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
|
Cell lines |
Bone-Marrow Derived Mast Cells |
|
Preparation Method |
Bone-Marrow Derived Mast Cells were stimulated with LPS (1 µg/ml) for 24 h and subsequently incubated with or without treatment of Compound 48/80 (50 µg/ml) for 5 min. Cells and culture supernatants were collected for the further analysis. |
|
Reaction Conditions |
Compound 48/80 (50 µg/ml);5min |
|
Applications |
Time-course analysis of dTCTP secretion by Compound 48/80 treatment demonstrated a rapid release of dTCTP within 5 min after Compound 48/80 treatment and persistent release of dTCTP during mast cell degranulation induced by Compound 48/80 [1]. |
| Animal experiment [2]: | |
|
Animal models |
Female BALB/c mice weighing 20–22 g |
|
Preparation Method |
Female BALB/c mice were randomly divided into the following 4 groups: the control, model.Thirty minutes after gavage, Compound 48/80 (0.3 mg/kg) was injected through the tail vein, and body temperature was recorded using a biological function experimental system, in which a probe was inserted into the anus of each mouse for 30 min. |
|
Dosage form |
0.3 mg/kg |
|
Applications |
In the analysis of Active Systemic Anaphylaxis, compared with the control group, the body temperature of the model group（Compound 48/80） decreased significantly. |
|
References: [1]. Cho H, Park J, et,al. Dimerized Translationally Controlled Tumor Protein-Binding Peptide 2 Attenuates Systemic Anaphylactic Reactions Through Direct Suppression of Mast Cell Degranulation. Front Pharmacol. 2021 Oct 19;12:764321. doi: 10.3389/fphar.2021.764321. PMID: 34737708; PMCID: PMC8560797. [2]. Zhang P, Wang Y, et,al. Allantoin Inhibits Compound 48/80-Induced Pseudoallergic Reactions In Vitro and In Vivo. Molecules. 2022 May 27;27(11):3473. doi: 10.3390/molecules27113473. PMID: 35684410; PMCID: PMC9182162. |
|
Compound 48/80 trihydrochloride is a mixture of condensation products of N-methyl-p-methoxyphenethylamine with formaldehyde[1].Compound 48/80 trihydrochloride is also a histamine releaser and a mast cell degranulator[2]. Compound 48/80 was first reported in 1951 as an active histamine-releasing agent[3] that can cause redness, itching, and itching of human skin [4]. Compound 48/80 was later used as a classical mast cell activator for IgE-independent G proteins and is the most commonly used activation method in pseudoallergy studies[5]. HIS secreted by mast cells induces vasodilation, edema, pruritus, and hypothermia. Compound 48/80 trihydrochloride (C48/80 trihydrochloride) inhibits both cytosolic and particulate phosphatidylinositol-specific phospholipase C activities with a similar efficiency; IC50 values are 2.1 μg/ml (supernatant) and 5.0 μg /ml (particulate fraction). The aggregation of human platelets induced by ADP and PAF-acether is inhibited by Compound 48/80[1].Compound 48/80 inhibits phosphatidylinositol-specific phospholipase C activity from human platelets[6].
In vitro，Time-course analysis of dTCTP secretion by Compound 48/80 treatment demonstrated a rapid release of dTCTP within 5 min after Compound 48/80 treatment and persistent release of dTCTP during mast cell degranulation induced by Compound 48/80[7].
In vivo，In In the analysis of systemic anaphylaxis, the body temperature of the model group (Compound 48/80) was significantly lower than that of the control group. Compound 48/80 induced increased serum concentrations of HIS, TNF-α and IL-8[8]. Compound 48/80-induced MC degranulation produced anticonvulsive effects against PTZ-induced epileptic seizures by extending the onset time of both myoclonic-jerk and generalized tonic–clonic seizure, and by shortening the duration of generalized tonic–clonic seizure[9].
复合物48/80三盐酸盐是N-甲基-p-甲氧基苯乙胺与甲醛缩合产物的混合物。它也是一种组胺释放剂和肥大细胞脱颗粒剂。复合物48/80最初于1951年被报道为一种能引起人类皮肤红斑、瘙痒和发痒的活性组胺释放剂。后来，它被用作IgE非依赖型G蛋白经典肥大细胞激活剂，并成为假过敏反应研究中最常用的激活方法之一。由肥大细胞分泌的组胺会引起血管扩张、水肿、瘙痒和低体温等反应。复合物48/80三盐酸盐可以抑制细胞质和颗粒态特异性磷脂酰肌醇酶C活性，其效率相似；IC50值分别为2.1μg/ml（上清液）和5.0μg/ml（颗粒部分）。同时，它还可以抑制ADP和PAF-acether诱导的人类血小板聚集，并且可以抑制来自人类血小板的特异性磷脂酰肌醇酶C活性。
在离体实验中，通过对Compound 48/80处理后dTCTP分泌的时间进程分析表明，在Compound 48/80处理后5分钟内迅速释放了dTCTP，并且在由Compound 48/80引起的肥大细胞脱颗粒过程中持续释放dTCTP。
在体内实验中，对于系统性过敏反应的分析显示，模型组（使用Compound 48/80）的体温明显低于对照组。Compound 48/80诱导了血清中HIS、TNF-α和IL-8浓度的增加。通过MC脱颗粒引起的抗惊厥效果可以延长PTZ诱发的肌阵挛和全身强直-阵挛性惊厥发作时间，并缩短全身强直-阵挛性惊厥持续时间。
References:
[1]: Bronner C, Wiggins C, et,al. Compound 48/80 is a potent inhibitor of phospholipase C and a dual modulator of phospholipase A2 from human platelet. Biochim Biophys Acta. 1987 Aug 15;920(3):301-5. doi: 10.1016/0005-2760(87)90108-1. PMID: 3607084.
[2]: Schemann M, Kugler EM, et,al.The mast cell degranulator compound 48/80 directly activates neurons. PLoS One. 2012;7(12):e52104. doi: 10.1371/journal.pone.0052104. Epub 2012 Dec 18. PMID: 23272218; PMCID: PMC3525567.
[3]: Wang J, Zhang Y, et,al.Resveratrol inhibits MRGPRX2-mediated mast cell activation via Nrf2 pathway. Int Immunopharmacol. 2021 Apr;93:107426. doi: 10.1016/j.intimp.2021.107426. Epub 2021 Feb 4. PMID: 33550032.
[4]: Ding Y, Che D, et,al.Quercetin inhibits Mrgprx2-induced pseudo-allergic reaction via PLCγ-IP3R related Ca2+ fluctuations. Int Immunopharmacol. 2019 Jan;66:185-197. doi: 10.1016/j.intimp.2018.11.025. Epub 2018 Nov 21. PMID: 30471617.
[5]: Wang J, Zhang Y, et,al.Paeoniflorin inhibits MRGPRX2-mediated pseudo-allergic reaction via calcium signaling pathway. Phytother Res. 2020 Feb;34(2):401-408. doi: 10.1002/ptr.6531. Epub 2019 Oct 31. PMID: 31667930.
[6]: Kaida S, Ohta Y, Imai Y, Ohashi K, Kawanishi M. Compound 48/80 causes oxidative stress in the adrenal gland of rats through mast cell degranulation. Free Radic Res. 2010 Feb;44(2):171-80. doi: 10.3109/10715760903380466. PMID: 19886753.
[7]: Cho H, Park J, et,al. Dimerized Translationally Controlled Tumor Protein-Binding Peptide 2 Attenuates Systemic Anaphylactic Reactions Through Direct Suppression of Mast Cell Degranulation. Front Pharmacol. 2021 Oct 19;12:764321. doi: 10.3389/fphar.2021.764321. PMID: 34737708; PMCID: PMC8560797.
[8]:Zhang P, Wang Y, et,al. Allantoin Inhibits Compound 48/80-Induced Pseudoallergic Reactions In Vitro and In Vivo. Molecules. 2022 May 27;27(11):3473. doi: 10.3390/molecules27113473. PMID: 35684410; PMCID: PMC9182162. et,al.
[9]:Kilinc E, Torun IE, et,al. Mast cell activation ameliorates pentylenetetrazole-induced seizures in rats: The potential role for serotonin. Eur J Neurosci. 2022 May;55(9-10):2912-2924. doi: 10.1111/ejn.15145. Epub 2021 Feb 23. PMID: 33565644.
| Cas No. | 848035-21-2 | SDF | |
| 别名 | C48/80 trihydrochloride | ||
| 化学名 | 4-methoxy-3,5-bis[[2-methoxy-5-[2-(methylamino)ethyl]phenyl]methyl]-N-methyl-benzeneethanamine, trihydrochloride | ||
| Canonical SMILES | COC1=CC=C(CCNC)C=C1CC2=CC(CCNC)=CC(CC3=C(OC)C=CC(CCNC)=C3)=C2OC.Cl.Cl.Cl | ||
| 分子式 | C32H45N3O3 • 3HCl | 分子量 | 629.1 |
| 溶解度 | 100mM in water | 储存条件 | Store at -20°C, sealed storage, away from moisture ,protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.5896 mL | 7.9479 mL | 15.8957 mL |
| 5 mM | 0.3179 mL | 1.5896 mL | 3.1791 mL |
| 10 mM | 0.159 mL | 0.7948 mL | 1.5896 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Inhibition of Compound 48/80 induced mediator release following oral administration of tiaramide hydrochloride in normal subjects
Ann Allergy 1983 Sep;51(3):367-70.PMID:6614599doi
The ability of tiaramide hydrochloride (RHC 2592) to inhibit cutaneous reactivity was studied using 11 normal volunteers. After repeated administration tiaramide hydrochloride inhibited cutaneous mast cell mediator release induced by Compound 48/80 while not affecting histamine-induced cutaneous reactivity. This is the first demonstration in man of an oral agent with such an effect.
The anti-anaphylactic action of tiaramide hydrochloride
Allergy 1978 Apr;33(2):76-81.PMID:80140DOI:10.1111/j.1398-9995.1978.tb01512.x.
Tiaramide hydrochloride (THC) is a new basic, non-steroidal, anti-flammatory drug. Its anti-anaphylactic action has been investigated using rat mast cells. It was found that THC exerts a strong inhibitory action on antigen-induced and compound 48/80-induced histamine release from rat peritoneal mast cells in a fluorometric assay. Compound 48/80-induced vasodilatation in rat skin is inhibited by prior intradermal injection of THC, as measured by blueing of skin due to intravascular Evans blue dye. THC also inhibits radio-labeled serotonin release from compound 48/80-challenged rat mast cells. In these experimental systems a similar action was exerted by disodium cromoglycate, but higher drug concentrations were needed. Further studies are needed to determine the exact mode of action of this drug and its eventual clinical use in the field of allergic diseases.
Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock
Braz J Med Biol Res 2020 Mar 2;53(3):e8853.PMID:32130289DOI:10.1590/1414-431X20198853.
Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by Compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.
Roxatidine attenuates mast cell-mediated allergic inflammation via inhibition of NF-κB and p38 MAPK activation
Sci Rep 2017 Jan 31;7:41721.PMID:28139747DOI:10.1038/srep41721.
Roxatidine is an active metabolite of roxatidine acetate hydrochloride which is a histamine H2-receptor antagonist that is used to treat gastric and duodenal ulcers. In this study, we investigated the anti-allergic inflammatory effects and the underlying molecular mechanism of roxatidine in phorbol 12-myristate 13-acetate and calcium ionophore (PMACI)-stimulated human mast cells-1 (HMC-1), compound 48/80-induced anaphylactic animal model and chemical allergen-induced contact hypersensitivity (CHS) models. Roxatidine suppressed the mRNA and protein expression of inflammatory cytokines such as TNF-α, IL-6, and IL-1β in PMACI-stimulated HMC-1 and compound 48/80-induced anaphylactic mice. In addition, roxatidine attenuated PMACI-induced nuclear translocation of NF-κB and the phosphorylation of MKK3/6 and MK2, which are both involved in the p38 MAPK pathway. Furthermore, we observed that roxatidine suppressed the activation of caspase-1, an IL-1β converting enzyme, in PMACI-stimulated HMC-1 and compound 48/80-induced anaphylactic mice. In CHS model, roxatidine significantly reduced ear swelling, increased number of mast cells, production levels of cytokines and migration of dendritic cells. Our findings provide evidence that the anti-allergic inflammatory properties of roxatidine are mediated by the inhibition of NF-κB and caspase-1 activation, p38 MAPK pathway and mast cell-derived cytokine production. Taken together, the in vitro and in vivo anti-allergic inflammatory effects suggest a possible therapeutic application of roxatidine in allergic inflammatory diseases.
Absorption-enhancing mechanism of sodium caprate and decanoylcarnitine in Caco-2 cells
J Pharmacol Exp Ther 1995 Feb;272(2):739-43.PMID:7853188doi
The mechanism of action of the absorption enhancers such as sodium caprate (C10) and decanoylcarnitine (DC) was examined. Both C10 and DC increased the epithelial permeability of fluorescein isothiocyanate dextran 4000 and decreased the transepithelial electrical resistance in Caco-2 cell monolayer. Irrespective of the presence or absence of mucosal calcium, C10 rapidly increased intracellular calcium levels dose-dependently. Compound 48/80, a phospholipase C inhibitor, prevented the increases of the intracellular calcium level and permeability of fluorescein isothiocyanate dextran 4000 by C10. Furthermore, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride, a strong calmodulin inhibitor, also significantly decreased the enhancing effect of C10. These results suggest that C10 releases calcium from intracellular stores via activation of phospholipase C in plasma membrane. The increase of the calcium levels was considered to induce the contraction of calmodulin-dependent actin microfilament, followed by dilatation of the paracellular route. Although DC also increased intracellular calcium levels, neither Compound 48/80 nor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride decreased the enhancing effect of DC. The enhancing mechanisms were different for C10 and DC.