Disease relevance of Hextol

• Propentofylline at a dose of 20 mg/kg intraperitoneally, but not at a dose of 10 mg/kg, significantly potentiated the protective effect of preconditioning ischemia in the CA1 hippocampal neurons [1].
• The results correspond to experimental data showing that propentofylline improves energy metabolism in cerebral ischemia [2].
• Consistently, propentofylline attenuated the development of hyperalgesia and the expression of spinal analgesic tolerance to morphine [3].
• PTX, HWA-448, HWA-285, and A81-3138 at doses of 200, 100, 100, and 50 to 75 mg/kg, respectively, were toxic as shown by worsened weight loss and increased mortality in animals when compared with infected animals without drug [4].
• These findings along with our earlier observations of an anti-allodynic activity of propentofylline using the identical animal model of mononeuropathy supports the concept that modulation of glial and neuroimmune activation may be potential therapeutic targets to treat or prevent neuropathic pain [5].

Psychiatry related information on Hextol

• Economic impact of introducing propentofylline for the treatment of dementia in Sweden [6].
• Propentofylline as a therapeutic agent to Alzheimer's disease is discussed [7].
• Propentofylline improves learning and memory deficits in rats induced by beta-amyloid protein-(1-40) [8].
• To investigate the pharmacological effects of propentofylline in vivo, we induced amnesia in rats by infusing anti-NGF antibody into the septum for 16 days [9].
• In contrast, psychometric assessments and the cognitive difficulties scale failed to demonstrate a therapeutic benefit of propentofylline after three months [10].

High impact information on Hextol

• Two of these, propentofylline and AIT-082, are trophic effectors in animals, increasing production of neurotrophic factors in brain and spinal cord [11].
• Activation of p38 and p42/44 MAP kinases in spinal cord ipsilateral to constriction injury was reduced by antagonists of NMDA, VPAC2 and NK2 (but not related) receptors, the glial inhibitor propentofylline and inhibitors of TNF-alpha [12].
• Propentofylline was administered 24 hours after short preconditioning ischemia, and animals were subjected to 5-minute ischemia 24 hours thereafter [1].
• Modulation of intracellular formation of reactive oxygen intermediates in peritoneal macrophages and microglia/brain macrophages by propentofylline [13].
• Propentofylline at the therapeutic concentration of 50 microM completely inhibited the Ca(2+)-dependent Con A-induced increase in the production of reactive oxygen intermediates in peritoneal macrophages [13].

Chemical compound and disease context of Hextol

• The xanthine derivative propentofylline (HWA 285) has been reported to show protective effects against neuronal damage induced by cerebral ischemia [14].
• A further reinforcement of the homeostatic adenosine effects on glial cells by pharmaca, such as propentofylline, may add to neuroprotection in Alzheimer's disease [15].
• IMPLICATIONS: This study demonstrates and provides biochemical evidence that preemptive inhibition of proinflammatory cytokine synthesis by local administration of pentoxifylline and propentofylline is useful in antagonizing hyperalgesia in formalin-induced pain [16].
• Twenty minutes before the onset of ischemia, either 1 mg/kg CPA, 5 mg/kg propentofylline, or 20 mg/kg theophylline were administered intravenously [17].
• An adenosine uptake blocker, propentofylline, reduces glutamate release in gerbil hippocampus following transient forebrain ischemia [18].

Biological context of Hextol

• Ischemia-induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the Mongolian gerbil and protection by propentofylline (HWA 285) [19].
• A phorbol 12-myristate 13-acetate-induced rise in the respiratory burst activity could not be inhibited by propentofylline in either cell type [13].
• Currently, we evaluated the effect of propentofylline (PPF), an experimental antiallodynic agent, on the phenotype and glutamate transporter expression of astrocytes [20].
• Pharmacokinetic characteristics of the drugs were similar except that HWA-285 produced lower concentrations in serum and A81-3138 showed a dose-dependent kinetics (longer half-life at a higher dose) [4].
• HWA 285 (57 mumol.h-1) slightly but significantly increased blood pressure, but did not affect heart rate, cardiac output or minute work [21].

Anatomical context of Hextol

• To evaluate a possible mechanism of neuroprotection by propentofylline, we studied its effect on the cellular production of reactive oxygen intermediates in microglial cells, which under pathological conditions can differentiate into brain macrophages, in comparison to peritoneal macrophages [13].
• Determination of the dose-response relation revealed the optimal dose of HWA 285 to be 10 mg/kg i.p. The effect of the drug on delayed selective nerve cell damage in the hippocampus was assessed by measuring the intensity of Nissl staining in the CA1 area by means of densitometry 4 days after a 10-minute occlusion [22].
• Neither the astrocytic response nor the neuronal calcium accumulation were observed in gerbils pretreated with propentofylline, HWA 285 (10 mg/kg, i.p.) 15 min before bilateral carotid artery occlusion [19].
• Anti-hyperalgesic and morphine-sparing actions of propentofylline following peripheral nerve injury in rats: mechanistic implications of spinal glia and proinflammatory cytokines [5].
• Myocardial capillary density (capillaries per mm2, means +/- SE) was 3092 +/- 97 in the adenosine infused group and 2870 +/- 153 in the HWA 285 infused group compared with 2426 +/- 93 in the controls, ie an increase of 27% (p less than 0.001) and 18% (p less than 0.02) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[21]

Associations of Hextol with other chemical compounds

• In a randomized double-blind placebo-controlled study in 30 patients with acute ischemic stroke, the effect of the adenosine uptake blocker propentofylline on regional brain glucose metabolism (rCMRglu) was investigated using repeated positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) [2].
• In contrast to HWA 285, pentobarbital provided no detectable protection of the CA1 neurons in our experimental model when administered 1 hour after occlusion, suggesting different mechanisms of action [22].
• We show here that a glial modulator propentofylline (PPF) dramatically diminished the activation of astrocytes induced by drugs of abuse, such as methamphetamine (METH) and morphine (MRP) [23].
• 1. The effect of a new xanthine derivate 1-5' oxohexyl-3-methyl-7-propylxanthine (HWA 285) was studied on heart performance in dogs and rabbits and on regional blood flow in rabbits [24].
• Except for propentofylline, which exhibited a marked selectivity toward the rolipram-sensitive PDE versus the cGMP-inhibited PDE III, the other xanthines modestly (IC50 in the 10(-4) M range) inhibited both cAMP-specific isoforms with similar potency [25].

Gene context of Hextol

• When PBMCs were cultured with propentofylline in vitro, the production of IL-6 was markedly increased at concentrations of 0.1 to 3.0 mmol/L of propentofylline and the production of IL-1 beta was slightly increased at concentrations of 1.0 to 3.0 mmol/L [26].
• We measured APP products and mRNAs for NGF and its low-affinity receptor p75 in 10-month-old Tg2576 whole brain after dietary propentofylline (PPF) or acetyl-L-carnitine (ALCAR) for 4 weeks to induce NGF- or p75-expression, respectively [27].
• Intriguingly, propentofylline blocked both the apoptotic features induced by beta42 and further induced an anti-apoptotic protein, Bcl-2, during a short time of incubation [7].
• Effects of propentofylline on tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant production in rats with cerulein-induced pancreatitis and endotoxemia [28].
• 7. In separate in vitro experiments, propentofylline did not inhibit adenosine deaminase activity [29].

Analytical, diagnostic and therapeutic context of Hextol

• In the present study, microfluorometry was used to investigate the effect of propentofylline on the hypoxia-hypoglycemia-induced intracellular calcium accumulation in gerbil hippocampal slices [14].
• Propentofylline (1, 5, 10 and 20 mg/kg) was administered intravenously, immediately after reperfusion and the animals recovered for 4 days [30].
• In another preventative paradigm, propentofylline (0.1, 1, or 10 microg) was administered daily intrathecally via direct lumbar puncture [31].
• 4. Regional blood flow (studied by use of 15 micrometers labelled microspheres) was increased in the heart, brain and skeletal muscle; the increase was dose-dependent in the range 0.3, 1.0 and 3.0 mg HWA 285 per kg intravenously [24].
• Oral administration of propentofylline, a stimulator of nerve growth factor (NGF) synthesis, recovers cholinergic neuronal dysfunction induced by the infusion of anti-NGF antibody into the rat septum [9].

References