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- 1. 脳血管性認知症の治療および予防 treatment and prevention of vascular dementia
English Journal
- Chronic Administration of the Methylxanthine Propentofylline Impairs Reinstatement to Cocaine by a GLT-1-Dependent Mechanism.
- Reissner KJ1, Brown RM2, Spencer S1, Tran PK1, Thomas CA1, Kalivas PW1.Author information 1Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.21] Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA [2] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.AbstractIn recent years, interactions between neurons and glia have been evaluated as mediators of neuropsychiatric diseases, including drug addiction. In particular, compounds that increase expression of the astroglial glutamate transporter GLT-1 (N-acetylcysteine and ceftriaxone) can decrease measures of drug seeking. However, it is unknown whether the compounds that influence broad measures of glial physiology can influence behavioral measures of drug relapse, nor is it clear whether the upregulated GLT-1 is functionally important for suppressing of drug seeking. To address these questions, we sought to determine whether the glial modulator and neuroprotective agent propentofylline (PPF) modifies drug seeking in rats using a reinstatement model of cocaine relapse. We found that 7 days of chronic (but not acute) administration of PPF significantly decreased both cue- and cocaine-induced reinstatement of cocaine seeking. We next determined whether the effect of systemic PPF on reinstatement depended upon its ability to restore expression of GLT-1 in the nucleus accumbens. PPF restored the cocaine-induced decrease in GLT-1 in the accumbens core; then, using an antisense strategy against glutamate transporter GLT-1, we found that restored transporter expression was necessary for PPF to inhibit cue-primed cocaine seeking. These findings indicate that modulating glial physiology with atypical xanthine derivatives like PPF is a potential avenue for developing new medications for cocaine abuse, and support the hypothesis that neuron-glial interactions contribute to mechanisms of psychostimulant addiction, particularly via expression and function of astroglial glutamate transporters.
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.Neuropsychopharmacology.2014 Jan;39(2):499-506. doi: 10.1038/npp.2013.223. Epub 2013 Aug 29.
- In recent years, interactions between neurons and glia have been evaluated as mediators of neuropsychiatric diseases, including drug addiction. In particular, compounds that increase expression of the astroglial glutamate transporter GLT-1 (N-acetylcysteine and ceftriaxone) can decrease measures of
- PMID 23985782
- Effects of propentofylline on CNS remyelination in the rat brainstem.
- Fernandes Bondan E, de Fátima Monteiro Martins M, Menezes Baliellas DE, Monteiro Gimenez CF, Castro Poppe S, Martha Bernardi M.Author information Department of Environmental and Experimental Pathology, University Paulista, São Paulo, SP, Brazil; Department of Veterinary Medicine, University Cruzeiro do Sul, São Paulo, SP, Brazil.AbstractPropentofylline (PPF) is a xanthine derivative with pharmacological effects distinct from those of the classical methylxanthines. It depresses activation of microglial cells and astrocytes which is associated with neuronal damage during neural inflammation and hypoxia. The aim of this study was to evaluate whether PPF had the capacity of affecting glial cells behavior during the process of demyelination and remyelination following ethidium bromide (EB) gliotoxic injury. EB injection into the CNS is commonly used as an experimental demyelinating model inducing local oligodendroglial and astrocytic death, which results in primary demyelination, blood-brain barrier and glia limitans disruption and Schwann cells invasion. Sixty Wistar rats were divided into four different groups receiving 10 microlitres of 0.1% EB or 0.9% saline solution into the cisterna pontis and treated or not with the xanthine. PPF treatment was done using 12.5 mg/kg/day by the intraperitonial route for 31 days of the experimental period. The rats were euthanized from 7 to 31 days after EB injection and brainstem sections were collected and processed for light and transmission electron microscopy studies. Results from both groups were compared by using a semi-quantitative method developed for documenting in semithin sections the extent and nature of remyelination of demyelinating lesions. Results showed that PPF administration after EB injection significantly increased both oligodendroglial and Schwann cell remyelination at 31 days (mean remyelination scores of 3.67 ± 0.5 for oligodendrocytes and 1.27 ± 0.49 for Schwann cells) compared to untreated animals (scores of 3.19 ± 0.57 and 0.90 ± 0.33, respectively). Microsc. Res. Tech., 2013. © 2013 Wiley Periodicals, Inc.
- Microscopy research and technique.Microsc Res Tech.2013 Nov 1. doi: 10.1002/jemt.22308. [Epub ahead of print]
- Propentofylline (PPF) is a xanthine derivative with pharmacological effects distinct from those of the classical methylxanthines. It depresses activation of microglial cells and astrocytes which is associated with neuronal damage during neural inflammation and hypoxia. The aim of this study was to e
- PMID 24185688
- Vasorelaxant effect of propentofylline in isolated equine digital veins.
- Kabbesh N, Gogny M, Chatagnon G, Noireaud J, Desfontis JC, Mallem MY.Author information LUNAM Université Oniris, "UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle", Atlanpole-La Chantrerie, BP 40706, Nantes F-44307, France.AbstractWe evaluated the vasorelaxant effect of propentofylline (PPF), a methylxanthine derivative, and its mechanism of action in equine digital veins (EDVs). Cumulative concentration-response curves to PPF (1 nM-300 µM) were recorded in phenylephrine-precontracted EDV rings under different experimental conditions. PPF-induced relaxation was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (an adenosine receptor antagonist; 3 µM). PPF-induced relaxation was partially inhibited in the presence of L-NAME (a nitric oxide (NO) synthase inhibitor; 100 µM), ODQ (an inhibitor of soluble guanylyl cyclase; 30 µM) or Rp-8-Br-PET-cGMP-S (a protein kinase G inhibitor; 3 µM). It was not modified by indomethacin (a non-selective cyclooxygenase (COX) inhibitor; 10 µM), and was slightly potentiated by H-89 (a protein kinase A inhibitor; 2 µM). In endothelium-intact EDVs, PPF-induced relaxation was associated with a 2.4- and 24.1-fold increase in the tissue cGMP and cAMP content respectively. PPF (100 μM) did not shift the concentration-response curve to phenylephrine (1 nM-300 µM) but reduced the maximal effect. To investigate whether PPF can affect cAMP- and cGMP-induced relaxations, relaxation curves to forskolin (an activator of adenylate cyclase) and to sodium nitroprusside (SNP, a NO donor) were recorded in EDV rings pretreated with PPF (100 µM). PPF only slightly potentiated the forskolin-induced relaxation without affecting the SNP-induced relaxation. We demonstrated that PPF-induced relaxation in EDVs is partially endothelium-dependent. The PPF-induced relaxation partially occurred via NO release and both cAMP and cGMP generation, through COX-independent mechanisms but could also result from the inhibition of cAMP-phosphodiesterase activity for the highest concentrations.
- European journal of pharmacology.Eur J Pharmacol.2013 Oct 15;718(1-3):124-30. doi: 10.1016/j.ejphar.2013.09.003. Epub 2013 Sep 17.
- We evaluated the vasorelaxant effect of propentofylline (PPF), a methylxanthine derivative, and its mechanism of action in equine digital veins (EDVs). Cumulative concentration-response curves to PPF (1 nM-300 µM) were recorded in phenylephrine-precontracted EDV rings under different experimental c
- PMID 24051271
Japanese Journal
- ラットの肝温阻血再灌流障害に対するペントキシフィリンおよびプロペントフィリンの有用性
- 移植 38(6), 426-433, 2003-12-10
- NAID 10011977274
- アデノシン輸送阻害作用を有するプロペントフィリン前投与がヒツジ胎仔臍帯圧迫モデルにおける脳温変化に及ぼす影響
- 日本産科婦人科學會雜誌 53(7), 1071-1078, 2001-07-01
- NAID 110002117585
- Propentofylline投与によるラット背部皮弁のAdenosine Preconditioning効果の増強について
- 日形会誌 : 日本形成外科学会会誌 = Journal of Japan Society of Plastic and Reconstructive Surgery 20(5), 296-301, 2000-05-20
- NAID 10011319980
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