Propentofylline in the Treatment of Alzheimer’s Disease and Vascular Dementia: A Review of Phase III Trials

Abstract

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.

Down‐regulation of astrocytic GLAST by microglia‐related inflammation is abrogated in dibutyryl cAMP‐differentiated cultures

“…Besides, the present data indicate that increasing cAMP-dependent signaling cascades in astrocytes should be further considered for the development of potential treatments of neurological disorders involving neuroinflammation. Indeed, drugs belonging to the xanthine family such as propentofylline (a selective phosphodiesterase inhibitor), are endowed with neuroprotective properties, as several times demonstrated in animal models but also in Alzheimer's disease patients (Hartikka et al 1992;Wu et al 1999;Rother et al 1998). Studying the influence of these drugs on astrocyte functions certainly deserves further attention.…”

A 26-Week Analysis of a Double-Blind, Placebo-Controlled Trial of the Ginkgo biloba Extract EGb 761^® in Dementia

“…Following a strategy commonly applied at the time the trial was designed [17], the study enrolled the two most frequent types of dementia, i.e. AD and MID.…”

5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

“…However, considering the regionally different physiological roles of nucleosides in the brain, regional differences in the nucleoside system and its changes in affected brain areas may be related to the development of CNS diseases as previously discussed [11]. Moreover, regional differences were demonstrated in the nucleoside system of human brain areas implicated in several CNS diseases in which different drugs effects on the nucleoside system are or may be used later in treatment of the following CNS diseases ( [186,317,318]. In addition, Urd and/or Guo and Ino may also have therapeutic potential against epilepsy, pain, anxiety, schizophrenia, sleep disorders, ischemic injury, multiple sclerosis, Alzheimer's disease and Parkinson's disease, among others [3,6,79,[319][320][321][322][323][324][325][326][327][328][329][330][331][332][333][334][335].…”