Oxatomide
(Synonyms: 欧诗美锭) 目录号 : GC61401
Oxatomide是一种有效的具有口服活性的双重H1组胺受体(H1-histaminereceptor)和P2X7受体拮抗剂，具有抗组胺和抗过敏活性。Oxatomide几乎完全阻断人P2X7受体中ATP诱导的电流(IC50为0.95μM)。Oxatomide可抑制ATP诱导的Ca2+内流，IC50值为0.43μM，并且还抑制5-羟色胺(serotonin)。
Cas No.:60607-34-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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Oxatomide is a potent and orally active dual H1-histamine receptor and P2X7 receptor antagonist with antihistamine and anti-allergic activity. Oxatomide almost completely blocks the ATP-induced current in human P2X7 receptors (IC50 of 0.95 μM). Oxatomide inhibits ATP-induced Ca2+ influx with an IC50 value of 0.43 μM and also inhibits serotonin[1][2].
[1]. Kazuki Yoshida, et al. P2X7 receptor antagonist activity of the anti-allergic agent oxatomide. Eur J Pharmacol. 2015 Nov 15;767:41-51. [2]. K Ohmori, et al. Pharmacological studies on oxatomide (KW-4354). (7) Antagonistic effects on chemical mediators. Nihon Yakurigaku Zasshi. 1983 May;81(5):399-409.
| Cas No. | 60607-34-3 | SDF | |
| 别名 | 欧诗美锭 | ||
| Canonical SMILES | O=C1NC2=CC=CC=C2N1CCCN3CCN(C(C4=CC=CC=C4)C5=CC=CC=C5)CC3 | ||
| 分子式 | C27H30N4O | 分子量 | 426.55 |
| 溶解度 | DMSO: 250 mg/mL (586.10 mM) | 储存条件 | Store at -20°C |
| 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。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3444 mL | 11.722 mL | 23.4439 mL |
| 5 mM | 0.4689 mL | 2.3444 mL | 4.6888 mL |
| 10 mM | 0.2344 mL | 1.1722 mL | 2.3444 mL |
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Oxatomide. A review of its pharmacodynamic properties and therapeutic efficacy
Drugs 1984 Mar;27(3):210-31.PMID:6200290DOI:10.2165/00003495-198427030-00003.
Oxatomide is an orally active H1-histamine receptor antagonist which, as appears to occur with some other antihistamines, also inhibits mast cell degranulation. Oxatomide has demonstrated response rates similar to those with other more established members of its drug class in a few studies of chronic urticaria and allergic rhinitis. Interestingly, some patients responding to Oxatomide were said to be unresponsive to previously administered antihistamines. The effect of Oxatomide was little different from placebo in clinical trials of bronchial asthma in adults. While somewhat more encouraging results have been reported in children with bronchial asthma when higher than presently recommended dosages were employed, and in follicular conjunctivitis, atopic dermatitis and food allergy, reports to date are largely preliminary in nature and additional well-controlled studies are needed to clarify the efficacy of Oxatomide in such conditions. The drug has been generally well tolerated, but shares some of the familiar H1-histamine receptor antagonist side effects. As with other similarly acting drugs, the 2 primary side effects with Oxatomide are drowsiness and weight gain. Thus, on the basis of present evidence, a trial with Oxatomide seems a potentially useful alternative in patients with conditions known or thought to be allergic in nature, in whom more established treatments were ineffective or poorly tolerated.
Oxatomide for stable asthma in adults and children
Cochrane Database Syst Rev 2003;(2):CD002179.PMID:12804426DOI:10.1002/14651858.CD002179.
Background: Oxatomide is a histamine H1-receptor antagonist. As an oral agent, Oxatomide may be useful in managing asthma. Some guidelines recommend Oxatomide for long-term prophylaxis of asthma in children. There is no clear evidence whether children or adults with asthma benefit from Oxatomide. Objectives: To determine whether Oxatomide alone, or in combination with other interventions, results in better disease control in people with asthma. Search strategy: The Collaborative Airway Group register and Collaborations trial register CENTRAL were searched using terms: Oxatomide* OR Celtect OR Pinset OR KW-4354 OR Tincet. Reference lists of all relevant trials or review articles were checked. Enquiries were made of authors of included studies and relevant pharmaceutical companies. A search of 'Igaku Chuo Zasshi' and 'J-Medicine' were made using the following terms: Oxatomide (also in Japanese) or Celtect (also in Japanese) or KW-4354. Selection criteria: Studies were randomised, placebo-controlled trials and the interventions were Oxatomide or matched placebo given alone or in combination with other asthma-medication for at least 4 weeks. Data collection and analysis: Four independent reviewers performed assessments of methodological quality and extracted relevant data. Main results: Six studies are included in this review. Three studies were mainly conducted in adults, two were conducted in older children (5-16 years) and one in infants (18-25 months). Trial duration was 4 to 52 weeks. Doses of Oxatomide varied between studies, ranging from 1 mg/kg/day for infants to 180 mg/day for adults. Only data on adverse events was suitable for meta-analysis. Although PEF did not change significantly in any of the studies, the FVC and FEV1 improved significantly in two. There was no uniform change in symptom scores. There was no significant difference between Oxatomide and placebo treatment in use of inhaled corticosteroid or bronchodilator. Two studies showed significant improvement with Oxatomide as judged subjectively by physicians. Adverse events, analysed using data from 4 parallel and one cross over study, showed Oxatomide to be associated with a significantly higher risk of any adverse event (OR: 2.97, 95%CI: 1.69 to 5.22) and drowsiness (OR: 5.22,95%CI: 2.53 to 10.74). Reviewer's conclusions: There is no evidence to show that Oxatomide has a significant effect on the control of stable asthma. Some studies reported significant benefits in subjective parameters. There was improvement in some lung function outcomes reported, but this were not consistent across measures or studies and may represent reporting bias. Adverse events, including drowsiness, were significantly greater with Oxatomide than placebo.
Exploratory study of Oxatomide derivatives with high P2X7 receptor inhibitory activity
Bioorg Med Chem Lett 2022 Dec 1;77:129035.PMID:36283612DOI:10.1016/j.bmcl.2022.129035.
Various Oxatomide derivatives were designed and synthesized to develop novel P2X7 receptor (P2X7R) antagonists. Evaluation for in-vitro P2X7R antagonist assay showed that DPM-piperazine moiety of Oxatomide was required to maintain an inhibitory activity. The structure of both alkyl chains and aromatic head groups strongly affected P2X7R inhibitory activity, and the analogue, with C4-type saturated alkyl chain and a non-substituted or fluorine-substituted indole, was 7.3 to 6.4 times more potent as a P2X7R antagonist than Oxatomide.
[Protective effect of Oxatomide in infantile bronchial asthma. Double-blind study vs placebo]
Minerva Pediatr 1998 Jul-Aug;50(7-8):339-46.PMID:9973801doi
Background: This study has been designed to assess the protective effect of Oxatomide in allergic bronchial asthma of the seasonal type in young children. Methods: The study was carried out in a paediatric clinic; sixteen children divided into two balanced groups took Oxatomide in an oral suspension at the dosage of 1 mg/kg/day, or placebo for a period of 2 months. Eight patients (7 males, 1 female), aged 22 months +/- 2.83 (mean +/- SD) took Oxatomide in an oral suspension at the dosage of 1 mg/kg/day, while the other eight (3 males, 5 females; 22.13 months +/- 3.48) took placebo. Efficacy was assessed by monitoring cough, dyspnea at rest, dyspnea following exercise, wheezing, sleep disorders at baseline and after 15, 30 and 60 days of treatment, on the basis of a semiquantitative scale. All side effects were recorded. Results: Persistent coughing was significantly reduced (p < 0.05) after two weeks' treatment with Oxatomide. Sleep disorders and other symptoms remarkably improved. Dyspnea at rest and following exercise disappeared after 15 days' therapy, while the intensity of wheezing decreased after 30 days' active treatment. In all parameters examined, Oxatomide was significantly more active than placebo at the first examination (p < 0.05 and p < 0.01). Oxatomide was well tolerated and only 2 patients complained of drowsiness which required a reduction in dosage. Conclusions: Oxatomide, at the dose of 1 mg/kg/day, obtained a good control of respiratory symptoms.
Antiinflammatory effects of Oxatomide
J Investig Allergol Clin Immunol 1999 Jul-Aug;9(4):207-14.PMID:10513346doi
There is increasing evidence that histamine may have wider proinflammatory and immunomodulatory activities than previously reported. It may influence several functions of lymphocytes, monocytes, basophils and macrophages, modulating the release of inflammatory mediators and cytokines. These observations have aroused interest in the pharmacology and clinical applications of histamine H1 receptor antagonists and have led to the identification of novel antiinflammatory properties for this class of drugs. Oxatomide, initially characterized as an H1 antagonist, inhibits the secretion of several mediators of inflammation from human basophils and mast cells. In vitro Oxatomide inhibits the release of both preformed (histamine and tryptase) and de novo synthesized mediators (leukotriene C4 and prostaglandin D2). The inhibitory effect is not restricted to basophils and mast cells but is also evident on other inflammatory cells such as the neutrophils. In this cell, Oxatomide inhibits arachidonic acid mobilization, and leukotriene B4 and platelet-activating factor synthesis, presumably by reducing the activity of cytosolic phospholipase A2. These observations extend the pharmacological activities of Oxatomide beyond H1 receptor antagonism and suggest that this drug influences a variety of biochemical events in human inflammatory cells. These antiinflammatory activities help to explain its beneficial effect in various allergic and inflammatory disorders, including urticaria, allergic rhinitis and bronchial asthma.