Loratadine

Loratadine is a non- sedating antihistamine that acts as a selective inverse agonist of peripheral histamine H 1 receptors (K i = 35 nM). It is a second-generation antihistamine that is often used to treat allergy symptoms. It can inhibit immunologic release of inflammatory mediators[1-3].

Loratadine(75 µM loratadine;24 hours) pre-treatment of exponentially growing cells increased radiation-induced cytotoxicity[4]. Loratadine (10 µM) inhibited TRPV2-dependent responses in a primary culture of mouse endometrial stromal cells and attenuated cell proliferation and migration in cell proliferation and wound healing assays[5]. The expression of H1R was dose-responsively induced by Advanced glycation end products (AGEs) in chondrocytes. Treatment with loratadine((25/50 µM; 24 h) mitigated AGEs-induced oxidative stress, as revealed by suppressed production of mitochondrial ROS and the NADPH oxidase subunit NOX4[6].

Loratadine(5,10 mg/kg; p.o.) significantly reduced gastric bleeding in mice. Loratadine suppress inflammation by specifically targeting TAK1 and suppressing consequent AP-1 signaling pathway activation and inflammatory cytokine production[7]. In ICR mice, single oral administration of loratadine at a dose of 5 or 10 mg/kg significantly inhibited the dorsal scratching behavior induced by histamine or an antigen[8].

References:
[1]. AlMasoud N, Bakheit AH, et,al. Loratadine. Profiles Drug Subst Excip Relat Methodol. 2022;47:55-90. doi: 10.1016/bs.podrm.2021.10.002. Epub 2021 Dec 7. PMID: 35396016.
[2]. Kreutner W, Chapman RW, et,al. Antiallergic activity of loratadine, a non-sedating antihistamine. Allergy. 1987 Jan;42(1):57-63. doi: 10.1111/j.1398-9995.1987.tb02188.x. PMID: 2436504.
[3]. Hunto ST, Kim HG, et,al. Loratadine, an antihistamine drug, exhibits anti-inflammatory activity through suppression of the NF-kB pathway. Biochem Pharmacol. 2020 Jul;177:113949. doi: 10.1016/j.bcp.2020.113949. Epub 2020 Apr 3. PMID: 32251678.
[4]. Soule BP, Simone NL, et,al. Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines. Radiat Oncol. 2010 Feb 3;5:8. doi: 10.1186/1748-717X-5-8. PMID: 20128919; PMCID: PMC2829588.
[5]. Van den Eynde C, Held K, et,al. Loratadine, an antihistaminic drug, suppresses the proliferation of endometrial stromal cells by inhibition of TRPV2. Eur J Pharmacol. 2022 Aug 5;928:175086. doi: 10.1016/j.ejphar.2022.175086. Epub 2022 Jun 14. PMID: 35714693.
[6]. Gao F, Zhang S. Loratadine Alleviates Advanced Glycation End Product-Induced Activation of NLRP3 Inflammasome in Human Chondrocytes. Drug Des Devel Ther. 2020 Jul 21;14:2899-2908. doi: 10.2147/DDDT.S243512. PMID: 32801633; PMCID: PMC7382759.
[7].Jang J, Hunto ST, et,al. Anti-Inflammatory Activities of an Anti-Histamine Drug, Loratadine, by Suppressing TAK1 in AP-1 Pathway. Int J Mol Sci. 2022 Apr 3;23(7):3986. doi: 10.3390/ijms23073986. PMID: 35409346; PMCID: PMC8999734.
[8]. Hossen MA, Fujii Y, et,al. Effect of loratadine on mouse models of atopic dermatitis associated pruritus. Int Immunopharmacol. 2005 Jul;5(7-8):1331-6. doi: 10.1016/j.intimp.2005.02.004. Epub 2005 Mar 9. PMID: 15914337.

氯雷他定Loratadine是一种非镇静性抗组胺药,作用于选择性的外周组胺H1受体的反向激动剂(Ki=35 nM)。它是第二代抗组胺药,常用于治疗过敏症状。它可以抑制免疫学释放炎症介质[1-3]。

Loratadine(75 µM loratadine;24 hours)对指数生长的细胞进行预处理可增加辐射引起的细胞毒性[4]。Loratadine (10 µM) 可以抑制小鼠子宫内膜基质细胞的TRPV2依赖性反应,并在细胞增殖和伤口愈合试验中减弱细胞增殖和迁移[5]。晚期糖基化终产物(AGEs)可以剂量依赖性诱导软骨细胞中H1R表达。Loratadine (25/50 µM；24 h)的处理可以缓解AGEs诱导的氧化应激,表现为抑制线粒体ROS和NADPH氧化酶亚基NOX4的产生[6]。

Loratadine(5,10 mg/kg; p.o.)可以显著减少小鼠的胃出血。Loratadine通过特异性靶向TAK1并抑制随后的AP-1信号通路激活和炎症细胞因子的产生来抑制炎症[7]。在ICR小鼠中,单次口服5或10 mg/kg的Loratadine可以显著抑制组胺或抗原诱导的背部抓痒行为[8]。