Timegadine (SR1368)
(Synonyms: 替美加定; SR1368) 目录号 : GC31965
Timegadine (SR1368) 是一种新型抗炎剂，被发现是一种有效的、竞争性的环加氧酶 (COX) 和脂加氧酶抑制剂，IC50 范围为 5 nM（洗涤过的兔血小板）至 20 μM（大鼠脑） ) 用于 COX 和 100 μ；M 用于马血小板匀浆的胞质溶胶部分和洗涤过的兔血小板中的脂加氧酶。
Cas No.:71079-19-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Female inbred Lewis rats (body weight ~150 g) are used in adjuvant arthritis and experimental allergic encephalomyelitis experiments. Paw volume is determined by mercury displacement plethismometer. Timegadine is administered orally in a volume of 1 mL/kg body weight, suspended in 0.5% carboxymethylcellulose[1]. |
References: [1]. George S, et al. The influence of food intake on the bioavailability of timegadine, a novel non-steroidal anti-inflammatory drug. Br J Clin Pharmacol. 1983 Apr;15(4):495-8. | |
Timegadine, a new antiinflammatory agent, is found to be a potent, competitive inhibitor of cyclo-oxygenase (COX) and lipo-oxygenase, with IC50s ranging from 5 nM (washed rabbit platelets) to 20 μM (rat brain) for COX and 100 μM for lipo-oxygenase both in the cytosol fraction of horse platelet homogenates, and in washed rabbit platelets.
Timegadine, a new antiinflammatory agent, is found to be a potent, competitive inhibitor of of COX and lipo-oxygenase, with IC50s ranging from 5 nM (washed rabbit platelets) to 20 μM (rat brain) for COX and 100 μM for lipo-oxygenase both in the cytosol fraction of horse platelet homogenates, and in washed rabbit platelets[2].
Timegadine, a new antiinflammatory agent, is found to be a potent, competitive inhibitor of prostaglandin synthetase which also inhibits cyclo-oxygenase (COX) and lipoxygenase. Daily oral doses of 10 to 30 mg/kg of Timegadine significantly inhibit both the primary and secondary lesions of adjuvant arthritis when the treatment is initiated on the day of the disease induction and continues for 28 days. Timegadine is able specifically to prevent the development of the swelling of the non-injected paw until 28 days after the adjuvant injection when administered for 5 days prior to and 5 days after the induction of the disease, in analogy with the effect of cyclophosphamide[1].
[1]. George S, et al. The influence of food intake on the bioavailability of timegadine, a novel non-steroidal anti-inflammatory drug. Br J Clin Pharmacol. 1983 Apr;15(4):495-8. [2]. Ahnfelt-R?nne I, et al. A new antiinflammatory compound, timegadine (N-cyclohexyl-N"-4-[2-methylquinolyl]-N'-2-thiazolylguanidine), which inhibits both prostaglandin and 12-hydroxyeicosatetraenoic acid (12-HETE) formation. Biochem Pharmacol. 1980 Dec;29(24):3265-9.
| Cas No. | 71079-19-1 | SDF | |
| 别名 | 替美加定; SR1368 | ||
| Canonical SMILES | CC1=NC2=CC=CC=C2C(/N=C(NC3CCCCC3)/NC4=NC=CS4)=C1 | ||
| 分子式 | C20H23N5S | 分子量 | 365.5 |
| 溶解度 | Soluble in DMSO | 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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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.736 mL | 13.6799 mL | 27.3598 mL |
| 5 mM | 0.5472 mL | 2.736 mL | 5.472 mL |
| 10 mM | 0.2736 mL | 1.368 mL | 2.736 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。
Timegadine: more than a non-steroidal for the treatment of rheumatoid arthritis. A controlled, double-blind study
Timegadine is a tri-substituted guanidine derivative which inhibits both arachidonate cyclo-oxygenase and lipoxygenase activity. In a 24-week randomized double-blind controlled trial, timegadine 500 mg/day was compared with naproxen 750 mg/day in two groups of 20 patients with active rheumatoid arthritis. In the timegadine group, significant improvements were seen in both biochemical and clinical markers of disease activity, i.e. ESR, serum IgG and IgM, leukocyte and platelet counts, duration of morning stiffness, Ritchie index, number of swollen joints, pain, and general condition. In the naproxen group, only the Ritchie index improved. Differences between treatments, when present, were always in favour of timegadine. Serum alkaline phosphatase rose during the first 8 weeks of treatment in the timegadine group. A transient rise was also seen in the naproxen group. The side effects reported were mainly gastrointestinal and allergic, the latter being more frequently found in the timegadine group. Timegadine is superior to naproxen in controlling disease activity in rheumatoid arthritis, and appears to possess disease-modifying properties.
The pharmacokinetics of timegadine and two of its metabolites after multiple oral dosing, and the effects of concomitant administration of ibuprofen
A 250 mg tablet of timegadine was given twice daily for 15 days to 13 healthy volunteers. On Day 16 a single morning dose of timegadine was supplemented by two 200 mg tablets of a proprietary brand of ibuprofen. Serum concentrations of timegadine were measured by high pressure liquid chromatography, and steady state was achieved between Days 5 and 8. Serum concentrations of two metabolites of timegadine, MI and MII were measured by thin layer chromatography by Leo Pharmaceutical Products, Denmark. Ibuprofen did not significantly affect the serum half-time of timegadine, but did reduce the maximum measured serum timegadine concentration, the area under the serum concentration versus time curve and the time to achieve maximum measured serum concentration. Serum liver enzymes remained within the normal ranges and there were no changes in hepatic microsomal enzyme activity as assessed by urinary excretion of D-glucaric acid.
A comparative trial of timegadine and D-penicillamine in rheumatoid arthritis
Forty-four patients with definite or classical rheumatoid arthritis were entered in a 48-week open study, comparing the long-term effects of Timegadine and D-penicillamine. Twenty-three and 21 patients were respectively allocated to the Timegadine and D-penicillamine groups. Two patients of the former group were lost for follow-up, soon after the first baseline. Thus data were available only for 42 patients, 21 in each group of whom eleven completed the 48-week period in each group. Seven patients in the Timegadine group stopped because of ineffectiveness, 2 because of skin eruption and 1 because of acute interstitial pneumonitis. In the D-penicillamine group, 9 patients dropped out: 3 because of proteinuria, 2 because of stomatitis, 1 because of dizziness and 1 because of headache. Pain (visual analogue scale), number of swollen and painful joints improved significantly in both groups (p less than 0.05). The acute phase reactants alpha1-acid-glycoprotein and ESR and the thrombocyte count significantly decreased in the penicillamine group (p less than 0.05). The other clinical, hematological and immunological tests did not change; neither did the liver and kidney function tests. The clinical results suggest that Timegadine is as effective as D-penicillamine in the treatment of rheumatoid arthritis. D-penicillamine takes advantage over Timegadine by decreasing significantly the acute phase reactants. However, Timegadine has a low profile of side-effects.
The protein binding of timegadine determined by equilibrium dialysis
The protein binding of timegadine to albumin, serum, plasma and plasma enriched with the acute phase reactants alpha 1-acid glycoprotein, alpha 1-anti-trypsin and C-reactive protein was determined by equilibrium dialysis. The effects of other analgesic and anti-inflammatories (indomethacin, ketoprofen, paracetamol and sodium salicylate) and other basic drugs (disopyramide, lignocaine, propranolol and quinidine) on the binding of timegadine were also determined. Timegadine binding was concentration-dependent up to 0.5 micrograms/ml, but independent above this level up to 10.0 micrograms/ml, the mean and standard error being 93.8 +/- 0.5%. Albumin accounted for only 32.4% of timegadine bound to plasma. Plasma enrichment with the acute phase reactants led to significant increases in timegadine binding. Simultaneous dialysis with other drugs caused significant decreases in timegadine binding.
The influence of food intake on the bioavailability of timegadine, a novel non-steroidal anti-inflammatory drug
The effects of food ingestion on the absorption of timegadine, a recently synthesised non-steroidal anti-inflammatory drug, was studied in ten healthy volunteers. It was found that food enhanced the absorption of timegadine as shown by increased peak plasma concentrations (Cmax), decreased time taken to achieve these concentrations (tmax), and increased area under the plasma concentration time curve (AUC).