Propentofylline in the Treatment of Vascular Dementia and Alzheimer-Type Dementia

Neurodegeneration refers to a large clinically and pathologically heterogeneous disease entity associated with slowly progressive neuronal loss in different anatomical and functional systems of the brain. Neurodegenerative diseases often affect cognition, e.g. Alzheimer's disease (AD), dementia with Lewy bodies and vascular dementia, or different aspects of the motor system, e.g., amyotrophic lateral sclerosis, Parkinson's disease and ataxic disorders. Owing to increasing knowledge about the mechanisms leading to neurodegeneration, the development of treatments able to modify the neurodegenerative process becomes possible for the first time. Currently, clinical outcome measures are used to assess the efficacy of such treatments. However, most clinical outcome measures have a low test-retest reliability and thus considerable measurement variance. Therefore, large patient populations and long observation times are needed to detect treatment effects. Furthermore, clinical outcome measures cannot distinguish between symptomatic and disease-modifying treatment effects. Therefore, alternative biomarkers including neuroimaging may take on a more important role in this process. Because MR scanners are widely available and allow for non-invasive detection and quantification of changes in brain structure and metabolism, there is increasing interest in the use of MRI/MRS to monitor objectively treatment effects in clinical trials of neurodegenerative diseases. Particularly volumetric MRI has been used to measure atrophy rates in treatment trials of AD because the relationship between atrophic changes and neuron loss is well established and correlates well with clinical measures. More research is needed to determine the value of other MR modalities, i.e. diffusion, perfusion and functional MRI and MR spectroscopy, for clinical trials with neuroprotective drugs.

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“…Similarly as for AD, an improvement in these parameters was found, which was correlated with a cognitive improvement (81,82).…”

Section: Spect and Pet In Vd Treatment Trialssupporting

confidence: 54%

Evaluation of treatment effects in Alzheimer's and other neurodegenerative diseases by MRI and MRS

2006

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“…The positive safety profile of long-term propentofylline treatment (Mielke et al, 1998) and its ability to spare morphine analgesia may have widespread clinical implications. Propentofylline may increase the options for opioid use to treat chronic pain; (a) by reducing opioid dose escalation, which is often associated with unwanted side effects (Raghavendra et al, 2003b), and (b) by attenuating the development of analgesic tolerance and hyperalgesia following chronic use of morphine.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Morphine Tolerance, Withdrawal-Induced Hyperalgesia, and Associated Spinal Inflammatory Immune Responses by Propentofylline in Rats

Raghavendra

Tanga

DeLeo

2003

Neuropsychopharmacol

230

175

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The activation of glial cells and enhanced proinflammatory cytokine expression at the spinal cord has been implicated in the development of morphine tolerance, and morphine withdrawal-induced hyperalgesia. The present study investigated the effect of propentofylline, a glial modulator, on the expression of analgesic tolerance and withdrawal-induced hyperalgesia in chronic morphine-treated rats. Chronic morphine administration through repeated subcutaneous injection induced glial activation and enhanced proinflammatory cytokine levels at the lumbar spinal cord. Moreover, glial activation and enhanced proinflammatory cytokine levels exhibited a temporal correlation with the expression of morphine tolerance and hyperalgesia. Consistently, propentofylline attenuated the development of hyperalgesia and the expression of spinal analgesic tolerance to morphine. The administration of propentofylline during the induction of morphine tolerance also attenuated glial activation and proinflammatory cytokines at the L5 lumbar spinal cord. These results further support the hypothesis that spinal glia and proinflammatory cytokines contribute to the mechanisms of morphine tolerance and associated abnormal pain sensitivity.

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“…These effects might be due to altered acetylcholine release by A 2A Rs (Cunha et al 1995 ;Jin and Fredholm 1997 ) . In addition to receptor antagonists, propentofylline, an inhibitor of "es" nucleoside transporters, has established neuroprotective effects , and its administration to patients with Alzheimer disease and vascular dementia resulted in functional improvements in clinical trials (Mielke et al 1998 ) .…”

Section: Dementiamentioning

confidence: 99%

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Kovács

Dobolyi

2012

Adenosine

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Nucleosides have a wide range of physiological and pathophysiological roles in the human brain as modulators of a variety of neural functions. For example, adenosine, inosine, guanosine, and uridine participate in the mechanisms underlying memory, cognition, sleep, pain, depression, schizophrenia, epilepsy, Alzheimer's disease, Huntington's disease, and Parkinson's disease. Consequently, increasing attention is now being given to the speci fi c role of nucleosides in physiological and pathological processes in the human brain. Different elements of nucleoside system, including nucleoside concentrations, metabolic enzyme activity, and expression of nucleoside transporters and receptors, may be changed under normal and pathological conditions. The alterations suggest that interlinked elements of the nucleoside system are functioning in a tightly concerted manner.Nucleoside levels, activity of nucleoside metabolic enzymes, and expression of nucleoside transporters and receptors are unevenly distributed in the brain, suggesting that nucleosides have different roles in functionally distinct human brain areas. The aim of this chapter is to summarize our present knowledge of the anatomical distribution of nucleoside system in the human brain, placing emphasis on potential therapeutic pharmacological strategies.

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Propentofylline in the Treatment of Vascular Dementia and Alzheimer-Type Dementia

Cited by 29 publications

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Evaluation of treatment effects in Alzheimer's and other neurodegenerative diseases by MRI and MRS

Evaluation of treatment effects in Alzheimer's and other neurodegenerative diseases by MRI and MRS

Attenuation of Morphine Tolerance, Withdrawal-Induced Hyperalgesia, and Associated Spinal Inflammatory Immune Responses by Propentofylline in Rats

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

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