Early closure of European Pimagedine trial

Keen, H.; Fukker, JH; Menzinger, G.

doi:10.1016/s0140-6736(97)26029-0

Cited by 24 publications

(4 citation statements)

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“…In experimental models of stroke, this drug can reduce the lesion volume in a dose dependent manner, acting even when administered 24h after the ischemic event [ 25 , 68 – 70 ]. However, this drug has been refrained from clinical trials due to safety reasons [ 71 ]. Other compounds have also been tested, such as 1400W, which has been shown to decrease lesion volume and neurological deficits after stroke in rats [ 72 ] but safety questions have also risen.…”

Section: Discussionmentioning

confidence: 99%

Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation

Jordan

Costa

Specker³

et al. 2023

PLoS ONE

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Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or in vivo. Target finding strategies such as in silico modelling and mass spectroscopy hint towards a direct interaction between C1 and the nitric oxide synthase making C1 a great candidate for specific intra-cellular interaction with the NO producing machinery.

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Section: Discussionmentioning

confidence: 99%

Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation

Jordan

Costa

Specker³

et al. 2023

PLoS ONE

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“…У Європі аміногуанідин не використовується з огляду на високу токсичність і здатність провокувати розвиток аутоімунних захворювань [23,24].…”

Section: блокатори рецепторів кпнгunclassified

Neuropathic pain: mechanisms of development, principles of diagnostics and treatment

Dmytriiev

Prudius

Zaletskaya

et al. 2019

PMJUA

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Neuropathic pain is a pain caused by a disease or focal damage to the somatosensory nervous system. The prevalence of chronic pain with neuropathic features in different countries is estimated at 7–10 %. Damages to the nervous system can occur at the level of peripheral nerves, plexus and dorsal roots (peripheral neuropathic pain) or spinal cord and brain (central neuropathic pain). Neuropathic pain is based on pathological activation of pain pathways. Neuropathic pain occurs with diabetic polyneuropathy more often than with all polyneuropathies of another etiology. Hyperglycemia is the major cause of chronic diabetes mellitus and its progression. Since the cause of pain can rarely be cured, treatment is usually symptomatic. Neuropathic pain is generally poorly controlled by analgesics. NB management is started with conservative pharmacotherapy before applying invasive analgesia. Although there are many drugs that can be used in patients with DPN, monotherapy can not always stop pain syndrome. In addition, the patient may not tolerate the full therapeutic dose of the drug. All this dictates the need for combination therapy.

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“…This may be because the focus of research has changed when companies have merged or because results from other trials have failed to indicate any favourable effects. Examples are the early closure for financial reasons of a trial aimed at protection of diabetic nephropathy [10], discontinuation of a secondary prevention trial after myocardial infarction with cardizem when generic compounds appeared on the market [11], and more versatile considerations such as ‘the current protocol did not meet the strategic direction in which [the company] wished to develop the drug’ [12]. …”

Section: Stopping a Stroke Trialmentioning

confidence: 99%

The Role of the Data Safety and Monitoring Committee in Stroke Trials

Asplund¹

2003

Eur Neurol

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There are many good reasons why any human experiment should have appropriate oversight. In clinical trials, the data safety and monitoring committee (DSMC) serves to protect the interests of the patients. In stroke trials, its members usually together represent a broad expertise in neurology, internal medicine, cardiology and biostatistics. Independency and integrity are key words, especially in the relationship to the sponsor of the trial. The DSMC members should have no long-term financial strings to the sponsor, and they should not be personally involved in patient recruitment and evaluation. The DSMC provides recommendations to the steering committee of the trial on whether to continue or to stop patient recruitment and on protocol amendments that may be necessary to protect the safety of the patients.

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Early closure of European Pimagedine trial

Cited by 24 publications

References 0 publications

Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation

Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation

Neuropathic pain: mechanisms of development, principles of diagnostics and treatment

The Role of the Data Safety and Monitoring Committee in Stroke Trials

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