Oxatomide is an orally active H1-receptor antagonist (antihistamine)[1-2]. Oxatomide is used in the treatment of allergic diseases such as allergic rhinitis, urticaria, and conjunctivitis[3-4].
In vitro, Oxatomide (1-10µM) was incubated with P-glycoprotein-expressing doxorubicin-resistant human leukemia K562/DXR cells for 45 minutes. Oxatomide significantly reversed the multidrug resistance phenotype in K562 cells and increased the intracellular accumulation of chemotherapeutic drugs[5]. Oxatomide (0.1–30µM) was used to pretreat mouse neuroblastoma N18TG2 cells, J774 macrophage cells, human myeloma RPMI8226 cells, and mouse bone marrow-derived mast cells (mBMMC) expressing functional P2X7 receptors for 1 minute, followed by stimulation with ATP (0.5–3mM) or BzATP (10–100µM). Oxatomide significantly inhibited P2X7 receptor-mediated calcium influx, membrane currents, mitogen-activated protein kinase (MAPK) activation, induction of inflammation-related genes, cell death (as measured by LDH release), and mast cell degranulation[6].
In vivo, Oxatomide (1.25–5mg/kg) was orally administered 4 hours prior to challenge to sensitized male Swiss strain mice that had been infected with Trichinella spiralisfor 30 to 40 days. Oxatomide dose-dependently and significantly prevented a lethal anaphylactic reaction induced by intravenous injection of Trichinella larval somatic antigens[7]. Oxatomide (100mg/kg) was administered as a single oral dose 30 minutes before the antigen challenge to passively sensitized WBB6F1-+/+ and B6D2F1 mice using a high dilution (1:128) of anti-bovine serum albumin (BSA) serum. Oxatomide inhibited the passive cutaneous anaphylaxis (PCA) reaction triggered by the high-dilution antiserum[8].
References:
[1] Hayashi K, Yanagi M, Wood-Baker R, et al. Oxatomide for stable asthma in adults and children. Cochrane Database Syst Rev. 2003;2003(2):CD002179.
[2] Richards DM, Brogden RN, Heel RC, et al. Oxatomide. A review of its pharmacodynamic properties and therapeutic efficacy. Drugs. 1984 Mar;27(3):210-31.
[3] Marone G, Granata F, Spadaro G, et al. Antiinflammatory effects of oxatomide. J Investig Allergol Clin Immunol. 1999 Jul-Aug;9(4):207-14.
[4] Yamagiwa N, Komine M, Hanaoka F, et al. Exploratory study of oxatomide derivatives with high P2X7 receptor inhibitory activity. Bioorg Med Chem Lett. 2022 Dec 1;77:129035.
[5] Ishikawa M, Fujita R, Furusawa S, et al. Circumvention of acquired resistance to doxorubicin in K562 human leukemia cells by oxatomide. Biol Pharm Bull. 2001 Oct;24(10):1185-7.
[6] Yoshida K, Ito M, Matsuoka I. P2X7 receptor antagonist activity of the anti-allergic agent oxatomide. Eur J Pharmacol. 2015 Nov 15;767:41-51.
[7] De Clerck F, Van Gorp L, Vanparijs O, et al. Oxatomide protects Trichinella spiralis infected mice from lethal anaphylaxis. Agents Actions. 1978 Dec;8(6):568-71.
[8] Kimura S, Watanabe A, Takeuchi M, et al, Drug susceptibility of PCA in WBB6F1-W/Wv mice. Cell Mol Life Sci. 1998 May;54(5):456-60.