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].
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.
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。