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Chemical Compound Review

Karsivan     3-methyl-1-(5-oxohexyl)-7- propyl-purine-2...

Synonyms: Hextol, Viviq, Propentofylina, Albert-285, Lopac-P-9689, ...
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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


High impact information on Hextol


Chemical compound and disease context of Hextol


Biological context of Hextol


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


Analytical, diagnostic and therapeutic context of Hextol


  1. Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor. Kawahara, N., Ide, T., Saito, N., Kawai, K., Kirino, T. J. Cereb. Blood Flow Metab. (1998) [Pubmed]
  2. Effect of propentofylline on regional cerebral glucose metabolism in acute ischemic stroke. Huber, M., Kittner, B., Hojer, C., Fink, G.R., Neveling, M., Heiss, W.D. J. Cereb. Blood Flow Metab. (1993) [Pubmed]
  3. Attenuation of morphine tolerance, withdrawal-induced hyperalgesia, and associated spinal inflammatory immune responses by propentofylline in rats. Raghavendra, V., Tanga, F.Y., DeLeo, J.A. Neuropsychopharmacology (2004) [Pubmed]
  4. Efficacy, toxicity, and pharmacokinetics of pentoxifylline and its analogs in experimental Staphylococcus aureus infections. Maderazo, E.G., Breaux, S., Woronick, C.L., Krause, P.J. Antimicrob. Agents Chemother. (1990) [Pubmed]
  5. Anti-hyperalgesic and morphine-sparing actions of propentofylline following peripheral nerve injury in rats: mechanistic implications of spinal glia and proinflammatory cytokines. Raghavendra, V., Tanga, F., Rutkowski, M.D., DeLeo, J.A. Pain (2003) [Pubmed]
  6. Economic impact of introducing propentofylline for the treatment of dementia in Sweden. Wimo, A., Witthaus, E., Rother, M., Winblad, B. Clinical therapeutics. (1998) [Pubmed]
  7. Propentofylline protects beta-amyloid protein-induced apoptosis in cultured rat hippocampal neurons. Koriyama, Y., Chiba, K., Mohri, T. Eur. J. Pharmacol. (2003) [Pubmed]
  8. Propentofylline improves learning and memory deficits in rats induced by beta-amyloid protein-(1-40). Yamada, K., Tanaka, T., Senzaki, K., Kameyama, T., Nabeshima, T. Eur. J. Pharmacol. (1998) [Pubmed]
  9. 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. Nitta, A., Ogihara, Y., Onishi, J., Hasegawa, T., Furukawa, S., Nabeshima, T. Behav. Brain Res. (1997) [Pubmed]
  10. Placebo-controlled trial of the xanthine derivative propentofylline in dementia. Möller, H.J., Maurer, I., Saletu, B. Pharmacopsychiatry (1994) [Pubmed]
  11. Trophic effects of purines in neurons and glial cells. Rathbone, M.P., Middlemiss, P.J., Gysbers, J.W., Andrew, C., Herman, M.A., Reed, J.K., Ciccarelli, R., Di Iorio, P., Caciagli, F. Prog. Neurobiol. (1999) [Pubmed]
  12. Activation of p38 and p42/44 MAP kinase in neuropathic pain: involvement of VPAC2 and NK2 receptors and mediation by spinal glia. Garry, E.M., Delaney, A., Blackburn-Munro, G., Dickinson, T., Moss, A., Nakalembe, I., Robertson, D.C., Rosie, R., Robberecht, P., Mitchell, R., Fleetwood-Walker, S.M. Mol. Cell. Neurosci. (2005) [Pubmed]
  13. Modulation of intracellular formation of reactive oxygen intermediates in peritoneal macrophages and microglia/brain macrophages by propentofylline. Banati, R.B., Schubert, P., Rothe, G., Gehrmann, J., Rudolphi, K., Valet, G., Kreutzberg, G.W. J. Cereb. Blood Flow Metab. (1994) [Pubmed]
  14. Effects of propentofylline on hypoxia-hypoglycemia-induced calcium accumulation in gerbil hippocampal slices. Kadoya, F., Mitani, A., Arai, T., Kataoka, K. J. Cereb. Blood Flow Metab. (1992) [Pubmed]
  15. Pathological immuno-reactions of glial cells in Alzheimer's disease and possible sites of interference. Schubert, P., Ogata, T., Miyazaki, H., Marchini, C., Ferroni, S., Rudolphi, K. J. Neural Transm. Suppl. (1998) [Pubmed]
  16. The effects of local pentoxifylline and propentofylline treatment on formalin-induced pain and tumor necrosis factor-alpha messenger RNA levels in the inflamed tissue of the rat paw. Dorazil-Dudzik, M., Mika, J., Schafer, M.K., Li, Y., Obara, I., Wordliczek, J., Przewłocka, B. Anesth. Analg. (2004) [Pubmed]
  17. Effects of adenosine agonists and an antagonist on excitatory transmitter release from the ischemic rabbit hippocampus. Martinez-Tica, J.F., Zornow, M.H. Brain Res. (2000) [Pubmed]
  18. An adenosine uptake blocker, propentofylline, reduces glutamate release in gerbil hippocampus following transient forebrain ischemia. Miyashita, K., Nakajima, T., Ishikawa, A., Miyatake, T. Neurochem. Res. (1992) [Pubmed]
  19. Ischemia-induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the Mongolian gerbil and protection by propentofylline (HWA 285). DeLeo, J., Toth, L., Schubert, P., Rudolphi, K., Kreutzberg, G.W. J. Cereb. Blood Flow Metab. (1987) [Pubmed]
  20. Induction of astrocyte differentiation by propentofylline increases glutamate transporter expression in vitro: heterogeneity of the quiescent phenotype. Tawfik, V.L., Lacroix-Fralish, M.L., Bercury, K.K., Nutile-McMenemy, N., Harris, B.T., Deleo, J.A. Glia (2006) [Pubmed]
  21. The effect of long-term vasodilatation on capillary growth and performance in rabbit heart and skeletal muscle. Ziada, A.M., Hudlicka, O., Tyler, K.R., Wright, A.J. Cardiovasc. Res. (1984) [Pubmed]
  22. Protection against ischemic brain damage using propentofylline in gerbils. DeLeo, J., Schubert, P., Kreutzberg, G.W. Stroke (1988) [Pubmed]
  23. Direct evidence of astrocytic modulation in the development of rewarding effects induced by drugs of abuse. Narita, M., Miyatake, M., Narita, M., Shibasaki, M., Shindo, K., Nakamura, A., Kuzumaki, N., Nagumo, Y., Suzuki, T. Neuropsychopharmacology (2006) [Pubmed]
  24. The effect of a xanthine derivative, 1-(5' oxohexyl)-3-methyl-7-propylxanthine (HWA 285), on heart performance and regional blood flow in dogs and rabbits. Hudlicka, O., Komarek, J., Wright, A.J. Br. J. Pharmacol. (1981) [Pubmed]
  25. Phosphodiesterase inhibitory profile of some related xanthine derivatives pharmacologically active on the peripheral microcirculation. Meskini, N., Némoz, G., Okyayuz-Baklouti, I., Lagarde, M., Prigent, A.F. Biochem. Pharmacol. (1994) [Pubmed]
  26. Differential effects of propentofylline on the production of cytokines by peripheral blood mononuclear cells in vitro. Miki, S., Miki, Y. Clinical therapeutics. (1991) [Pubmed]
  27. Effect of PPF and ALCAR on the induction of NGF- and p75-mRNA and on APP processing in Tg2576 brain. Chauhan, N.B., Siegel, G.J. Neurochem. Int. (2003) [Pubmed]
  28. Effects of propentofylline on tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant production in rats with cerulein-induced pancreatitis and endotoxemia. Sugita, H., Yamaguchi, Y., Ikei, S., Ogawa, M. Pancreas (1997) [Pubmed]
  29. Effect of propentofylline (HWA 285) on extracellular purines and excitatory amino acids in CA1 of rat hippocampus during transient ischaemia. Andiné, P., Rudolphi, K.A., Fredholm, B.B., Hagberg, H. Br. J. Pharmacol. (1990) [Pubmed]
  30. Effect of propentofylline (HWA 285) on metabolic and functional recovery in the spinal cord after ischemia. Danielisová, V., Chavko, M., Schubert, P.H. Neuropharmacology (1994) [Pubmed]
  31. Propentofylline, a glial modulating agent, exhibits antiallodynic properties in a rat model of neuropathic pain. Sweitzer, S.M., Schubert, P., DeLeo, J.A. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
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