Propentofylline
(Synonyms: 普罗潘非林,HWA 285) 目录号 : GC46208A xanthine derivative and neuroprotective agent
Cas No.:55242-55-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Propentofylline is a xanthine derivative and neuroprotective agent.1,2 It increases NGF production in primary mouse astroglia when used at concentrations ranging from 0.12 to 3.33 mM, with the maximum increase observed at 1.11 mM.1 Propentofylline (20 μg/ml) reduces cell death induced by amyloid-β (1-42) in primary rat hippocampal neurons.2 Intravenous infusion of propentofylline (0.01, 0.05, and 0.1 mg/kg per minute) reduces infarct volume in a rat model of ischemic brain damage induced by permanent middle cerebral artery occlusion (MCAO) when administered following MCAO.3 It inhibits cAMP phosphodiesterases, is an antagonist of adenosine A1 and A2 receptors, and binds to adenosine transporters.4,5
|1. Shinoda, I., Furukawa, Y., and Furukawa, S. Stimulation of nerve growth factor synthesis/secretion by propentofylline in cultured mouse astroglial cells. Biochem. Pharmacol. 39(11), 1813-1816 (1990).|2. Koriyama, Y., Chiba, K., and Mohri, T. Propentofylline protects β-amyloid protein-induced apoptosis in cultured rat hippocampal neurons. Eur. J. Pharmacol. 458(3), 235-241 (2003).|3. Park, C.K., and Rudolphi, K.A. Antiischemic effects of propentofylline (HWA 285) against focal cerebral infarction in rats. Neurosci. Lett. 178(2), 235-238 (1994).|4. Nagata, K., Ogawa, T., Omosu, M., et al. In vitro and in vivo inhibitory effects of propentofylline on cyclic AMP phosphodiesterase activity. Arzneimittelforschung 35(7), 1034-1036 (1985).|5. Fredholm, B.B., Fastbom, J., Kvanta, A., et al. Further evidence that propentofylline (HWA 285) influences both adenosine receptors and adenosine transport. Fundam. Clin. Pharmacol. 6(3), 99-111 (1992).
| Cas No. | 55242-55-2 | SDF | |
| 别名 | 普罗潘非林,HWA 285 | ||
| Canonical SMILES | CCCN(C=N1)C2=C1N(C)C(N(CCCCC(C)=O)C2=O)=O | ||
| 分子式 | C15H22N4O3 | 分子量 | 306.4 |
| 溶解度 | Acetonitrile: slightly soluble,Chloroform: slightly soluble | 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 | 3.2637 mL | 16.3185 mL | 32.6371 mL |
| 5 mM | 0.6527 mL | 3.2637 mL | 6.5274 mL |
| 10 mM | 0.3264 mL | 1.6319 mL | 3.2637 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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Propentofylline for dementia
Cochrane Database Syst Rev 2003;(2):CD002853.PMID:12804440DOI:10.1002/14651858.CD002853.
Background: Propentofylline is a novel therapeutic agent for dementia that readily crosses the blood-brain barrier and acts by blocking the uptake of adenosine and inhibiting the enzyme phosphodiesterase. In vitro and in vivo its mechanism of action appears to be twofold; it inhibits the production of free radicals and reduces the activation of microglial cells. It therefore interacts with the inflammatory processes that are thought to contribute to dementia, and given its mechanism of action is a possible disease modifying agent rather than a purely symptomatic treatment. Objectives: To determine the clinical efficacy and safety of Propentofylline for people with dementia. Search strategy: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 5 February 2003. Aventis, the manufacturing pharmaceutical company, was asked for data from unpublished studies but declined to enter into correspondence. Selection criteria: Unconfounded double-blind randomized controlled trials of Propentofylline compared with a placebo or another treatment group. Data collection and analysis: There were detailed reports of only four of the nine included studies. The efficacy of Propentofylline was reviewed for undifferentiated dementia as there were not enough data to attempt a subgroup analysis for the types of dementia. Main results: The following statistically significant treatment effects in favour of Propentofylline are reported. Cognition at 3, 6 and 12 months including MMSE at 12 months. [MD 1.2, 95%CI 0.12 to 2.28, P=0.03] Severity of dementia at 3, 6 and 12 months including CGI at 12 months [MD -0.21, 95%CI -0.39 to -0.03, P=0.03]. Activities of Daily Living (NAB) at 6 and 12 months [MD -1.20, 95%CI -2.22 to -0.18, P=0.02]. Global Assessment (CGI) at 3 months [MD -0.48, 95% CI -0.75 to -0.21, P=0.0006], but not at later times. Tolerability There were minimal data on adverse effects and drop-outs. There were a statistically significant treatment effects in favour of placebo at 12 months, for the number of dropouts, [OR=1.43, 95%CI 1.04 to 1.90, P=0.03]. Reviewer's conclusions: There is limited evidence that Propentofylline might benefit cognition, global function and activities of daily living of people with Alzheimer's disease and/or vascular dementia. The meta-analyses reported here are far from satisfactory as a summary of the efficacy of Propentofylline, considering the unpublished information on another 1200 patients in randomized trials that exists. Unfortunately Aventis has been unwilling to correspond with the authors, significantly limiting the scope of this review.
Propentofylline, a CNS glial modulator does not decrease pain in post-herpetic neuralgia patients: in vitro evidence for differential responses in human and rodent microglia and macrophages
Exp Neurol 2012 Apr;234(2):340-50.PMID:22119425DOI:10.1016/j.expneurol.2011.11.006.
There is a growing body of preclinical evidence for the potential involvement of glial cells in neuropathic pain conditions. Several glial-targeted agents are in development for the treatment of pain conditions. Here we report the failure of a glial modulating agent, Propentofylline, to decrease pain reported in association with post-herpetic neuralgia. We offer new evidence to help explain why Propentofylline failed in patients by describing in vitro functional differences between rodent and human microglia and macrophages. We directly compared the proinflammatory response induced by lipopolysaccharide (LPS) with or without Propentofylline using rat postnatal microglia, rat peritoneal macrophages, human fetal microglia, human peripheral macrophages and human immortalized THP-1 cells. We measured tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and nitrite release (as an indicator of nitric oxide (NO)) as downstream indicators. We found that LPS treatment did not induce nitrite in human microglia, macrophages or THP-1 cells; however LPS treatment did induce nitrite release in rat microglia and macrophages. Following LPS exposure, Propentofylline blocked TNF-α release in rodent microglia with all the doses tested (1-100 μM), and dose-dependently decreased TNF-α release in rodent macrophages. Propentofylline partially decreased TNF-α (35%) at 100 μM in human microglia, macrophages and THP-1 macrophages. Propentofylline blocked nitrite release from LPS stimulated rat microglia and inhibited nitrite in LPS-stimulated rat macrophages. IL-1β was decreased in LPS-stimulated human microglia following Propentofylline at 100 μM. Overall, human microglia were less responsive to LPS stimulation and Propentofylline treatment than the other cell types. Our data demonstrate significant functional differences between cell types and species following Propentofylline treatment and LPS stimulation. These results may help explain the differential behavioral effects of Propentofylline observed between rodent models of pain and the human clinical trial.
Propentofylline: glial modulation, neuroprotection, and alleviation of chronic pain
Handb Exp Pharmacol 2011;(200):235-50.PMID:20859798DOI:10.1007/978-3-642-13443-2_8.
Propentofylline is a unique methylxanthine with clear cyclic AMP, phosphodiesterase, and adenosine actions, including enhanced synaptic adenosine signaling. Both in vitro and in vivo studies have demonstrated profound neuroprotective, antiproliferative, and anti-inflammatory effects of Propentofylline. Propentofylline has shown efficacy in preclinical models of stroke, opioid tolerance, and acute and chronic pain. Clinically, Propentofylline has shown efficacy in degenerative and vascular dementia, and as a potential adjuvant treatment for schizophrenia and multiple sclerosis. Possible mechanisms of action include a direct glial modulation to decrease a reactive phenotype, decrease glial production and release of damaging proinflammatory factors, and enhancement of astrocyte-mediated glutamate clearance. This chapter reviews the literature that supports a myriad of protective actions of this small molecule and implicates Propentofylline as a potential therapeutic for the treatment of chronic pain. From these studies, we propose a CNS multipartite synaptic action of Propentofylline that includes modulation of pre- and postsynaptic neurons, astrocytes, and microglia in the treatment of chronic pain syndromes, including, but not limited to, neuropathic pain.
Propentofylline in the treatment of Alzheimer's disease and vascular dementia: a review of phase III trials
Dement Geriatr Cogn Disord 1998 Jul;9 Suppl 1:36-43.PMID:9716243DOI:10.1159/000051188.
Propentofylline, a neuroprotective glial cell modulator, has been shown in preclinical studies to address some of the common pathological processes of Alzheimer's disease (AD) and vascular dementia (VaD), including glial cell activation and increased production of cytokines, free radicals, and glutamate. To examine whether Propentofylline (300 mg t.i.d. taken 1 h before meals) would provide beneficial effects in patients with AD and/or VaD, 901 patients with mild-to-moderate AD and 359 patients with mild-to-moderate VaD were enrolled in four double-blind, placebo-controlled, randomized studies ranging in duration from 6 months to 56 weeks. Propentofylline was found to provide consistent improvements over placebo in efficacy assessments for both AD and VaD patients. In addition, results from a drug withdrawal study suggested that Propentofylline does not merely relieve dementia symptoms but slows the progression of the disease itself. Propentofylline had a good safety profile and was generally well tolerated.
Pentoxifylline, Propentofylline and pentifylline for acute ischaemic stroke
Cochrane Database Syst Rev 2000;(2):CD000162.PMID:10796310DOI:10.1002/14651858.CD000162.
Background: Methylxanthine derivatives are vasodilators. They also inhibit platelet aggregation and thromboxane A2 synthesis, decrease the release of free radicals and may be neuroprotective. Objectives: The objective of this review was to assess the effect of intravenous or oral methylxanthines (pentoxifylline, Propentofylline, or pentifylline) in patients with acute ischaemic stroke. Search strategy: We searched the Cochrane Stroke Group trials register, Medline (from 1965), Embase (from 1981), ISI (from 1981) and the Ottawa stroke trials registry. We contacted drug companies. Selection criteria: Randomised trials comparing pentoxifylline, Propentofylline or pentifylline with placebo or control in patients with definite or presumed acute ischaemic stroke. Trials were included if treatment was started within one week of stroke onset. Data collection and analysis: Two reviewers independently applied the inclusion criteria. Trial quality was assessed. Main results: Five trials were included. Four trials tested pentoxifylline in 763 people, and one tested Propentofylline in 30 people. No trials of pentifylline were found. Early death (within four weeks) occurred in 34 of 408 patients given a methylxanthine drug compared with 49 of 385 given placebo (odds ratio 0.64, 95% confidence interval 0.41 to 1.02). This non-significant trend to less deaths was due mainly to one pentoxifylline trial that found a highly significant reduction in early deaths. Two trials reported early death or disability and found a non-significant reduction (odds ratio 0.49, 95% confidence interval 0.20 to 1.20). Late death (beyond four weeks) was reported in the Propentofylline trial involving 30 patients, with no difference between treatment and placebo (odds ratio 0.70, 95% confidence interval 0.13 to 3.68). Data for neurological impairment and disability were not in a form suitable for analysis. Data on quality of life, stroke recurrence, thromboembolism and bleeding were not reported. Reviewer's conclusions: There is not enough evidence to assess the effectiveness and safety of methylxanthines after acute ischaemic stroke.