Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C15H22N4O3 |
| Molecular Weight | 306.3602 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCN1C=NC2=C1C(=O)N(CCCCC(C)=O)C(=O)N2C
InChI
InChIKey=RBQOQRRFDPXAGN-UHFFFAOYSA-N
InChI=1S/C15H22N4O3/c1-4-8-18-10-16-13-12(18)14(21)19(15(22)17(13)3)9-6-5-7-11(2)20/h10H,4-9H2,1-3H3
| Molecular Formula | C15H22N4O3 |
| Molecular Weight | 306.3602 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/15266424
http://www.ncbi.nlm.nih.gov/pubmed/9931990
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/15266424
http://www.ncbi.nlm.nih.gov/pubmed/9931990
Propentofylline is a selective inhibitor of adenosine transport and phosphodiesterase. For several years it has been well established in the geriatric therapy of the dog improving hemodynamics in cerebral and peripheral compartments. In human medicine clinical development of this pharmaceutical has already entered an advanced stage for the long-term therapy of patients with Alzheimer's disease and vascular dementia. In the brains of senile dogs and in human patients suffering from Alzheimer's disease comparable neuropathological findings can be made. In experimental models of vascular dementia and/or Alzheimer's disease it improves cognitive functions, inhibits inflammatory processes as well as excessive activation of microglia, formation of free radicals, cytocines and abnormal amyloid precursor proteins (APP). It stimulates synthesis and liberation of nerve growth factor (NGF) and reduces ischemic damage to the brain. In clinical studies in humans it improved cognitive functions as well as global functions and the ability to cope with tasks of routine daily life in patients suffering from Alzheimer's disease and vascular dementia. Possible mechanisms of action include a direct glial modulation to decrease a reactive phenotype, decrease glial production and release of damaging proinflammatory factors, and enhancement of astrocyte-mediated glutamate clearance. Net effects of propentofylline in vivo will be dependent on the concentrations of propentofylline and adenosine available and on the subtypes of adenosine receptors, phosphodiesterases, and nucleoside transporters present. In March, 2000 Aventis Pharma, announced that was discontinuing development of propentofylline as a possible treatment for Alzheimer's disease. The decision was a result of the company's portfolio review process which is intended to ensure that resources are devoted only to projects with a high potential for success.
Originator
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
828.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9868540/ |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROPENTOFYLLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
269.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9868540/ |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYPROPENTOFYLLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
508.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9868540/ |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROPENTOFYLLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
460.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9868540/ |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYPROPENTOFYLLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.74 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9868540/ |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROPENTOFYLLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.79 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9868540/ |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYPROPENTOFYLLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Decreased extracellular adenosine levels lead to loss of hypoxia-induced neuroprotection after repeated episodes of exposure to hypoxia. | 2013 |
|
| Anti-inflammatory effects and possible mechanism of action of lupeol acetate isolated from Himatanthus drasticus (Mart.) Plumel. | 2010-12-17 |
|
| Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus. | 2010-12-10 |
|
| Activation of astrocytes in the spinal cord contributes to the development of bilateral allodynia after peripheral nerve injury in rats. | 2010-12-02 |
|
| Synergetic analgesia of propentofylline and electroacupuncture by interrupting spinal glial function in rats. | 2010-11 |
|
| Pharmacological shift of the ambiguous nitric oxide action from neurotoxicity to cyclic GMP-mediated protection. | 2010-11 |
|
| Use of propentofylline in feline bronchial disease: prospective, randomized, positive-controlled study. | 2010-09-03 |
|
| Evidence for a role of endocannabinoids, astrocytes and p38 phosphorylation in the resolution of postoperative pain. | 2010-05-28 |
|
| Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo following peripheral nerve injury. | 2010-05 |
|
| Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats. | 2010-04-16 |
|
| TNF-alpha and neuropathic pain--a review. | 2010-04-16 |
|
| Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. | 2010-03-17 |
|
| Differential involvement of trigeminal transition zone and laminated subnucleus caudalis in orofacial deep and cutaneous hyperalgesia: the effects of interleukin-10 and glial inhibitors. | 2009-12-21 |
|
| Post herpetic neuralgia, schwann cell activation and vitamin D. | 2009-12 |
|
| Activation of p-38alpha MAPK contributes to neuronal hyperexcitability in caudal regions remote from spinal cord injury. | 2009-11 |
|
| Astrocyte activation and memory impairment in the repetitive febrile seizures model. | 2009-10 |
|
| Adenosine neuromodulation and traumatic brain injury. | 2009-09 |
|
| Release of adenosine and ATP during ischemia and epilepsy. | 2009-09 |
|
| Remote astrocytic and microglial activation modulates neuronal hyperexcitability and below-level neuropathic pain after spinal injury in rat. | 2009-07-07 |
|
| Pharmacological Treatment of Alzheimer's Disease: Is it Progressing Adequately? | 2009-04-02 |
|
| Natural non-trasgenic animal models for research in Alzheimer's disease. | 2009-04 |
|
| Vascular cognitive impairment. | 2009-01 |
|
| Microbial transformation of hydroxy metabolites of 1-oxohexyl derivatives of theobromine by Cunninghamella echinulata NRRL 1384. | 2009-01 |
|
| Disruption of glial function regulates the effects of electro-acupuncture at Tsusanli on gastric activity in rats. | 2009 |
|
| Effect of interleukin-1beta on spinal cord nociceptive transmission of normal and monoarthritic rats after disruption of glial function. | 2009 |
|
| Implication of activated astrocytes in the development of drug dependence: differences between methamphetamine and morphine. | 2008-10 |
|
| Differential migration, LPS-induced cytokine, chemokine, and NO expression in immortalized BV-2 and HAPI cell lines and primary microglial cultures. | 2008-10 |
|
| Propentofylline attenuates allodynia, glial activation and modulates GABAergic tone after spinal cord injury in the rat. | 2008-08-31 |
|
| Present and prospective clinical therapeutic regimens for Alzheimer's disease. | 2008-08 |
|
| Propentofylline-induced astrocyte modulation leads to alterations in glial glutamate promoter activation following spinal nerve transection. | 2008-04-09 |
|
| A placebo controlled study of the propentofylline added to risperidone in chronic schizophrenia. | 2008-04-01 |
|
| Modulation of microglia can attenuate neuropathic pain symptoms and enhance morphine effectiveness. | 2008-03-14 |
|
| p38 MAPK, microglial signaling, and neuropathic pain. | 2007-11-01 |
|
| The role of ATP and adenosine in the brain under normoxic and ischemic conditions. | 2007-09 |
|
| Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP. | 2007-07-20 |
|
| Reprint of "efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury" [Brain Behav. Immun. 21 (2007) 238-246]. | 2007-07 |
|
| Effects of interleukin-1beta on spinal cord nociceptive transmission in intact and propentofylline-treated rats. | 2007-05 |
|
| [Activation of astrocytes effects changes of substance P in cornu dorsal medullae spinalis in chronic prostatitis rats]. | 2007-04 |
|
| Chronic pain-induced astrocyte activation in the cingulate cortex with no change in neural or glial differentiation from neural stem cells in mice. | 2007-03-19 |
|
| Behavioural and morphological evidence for the involvement of glial cell activation in delta opioid receptor function: implications for the development of opioid tolerance. | 2007-03-12 |
|
| P1 receptors and cytokine secretion. | 2007-03 |
|
| Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury. | 2007-02 |
|
| Progress update: Pharmacological treatment of Alzheimer's disease. | 2007 |
|
| Recent advances in basic neurosciences and brain disease: from synapses to behavior. | 2006-12-30 |
|
| Direct evidence of astrocytic modulation in the development of rewarding effects induced by drugs of abuse. | 2006-11 |
|
| Induction of astrocyte differentiation by propentofylline increases glutamate transporter expression in vitro: heterogeneity of the quiescent phenotype. | 2006-08-15 |
|
| Propentofylline attenuates vincristine-induced peripheral neuropathy in the rat. | 2006-06-12 |
|
| mu-Opioid receptor internalization-dependent and -independent mechanisms of the development of tolerance to mu-opioid receptor agonists: Comparison between etorphine and morphine. | 2006 |
|
| Activation of p38 and p42/44 MAP kinase in neuropathic pain: involvement of VPAC2 and NK2 receptors and mediation by spinal glia. | 2005-12 |
|
| Neuroprotection by adenosine in the brain: From A(1) receptor activation to A (2A) receptor blockade. | 2005-06 |
Patents
Sample Use Guides
dose of propentofylline: 3 x 300 mg taken 1 hr before food
Route of Administration:
Oral
Primary astrocyte cultures, which represent an activated phenotype with a polygonal morphology and low GLT-1 expression, were treated for 3 or 7 days with 10, 100, or 1,000 uM propentofylline (PPF). PPF dose-dependently induced astrocytes to display a mature phenotype, with elongated processes and a stellate shape, as well as increased GLT-1 and GLAST immunoreactivity, similar to that seen with db-cAMP. Real time RT-PCR and Western blot analysis clearly demonstrated that PPF caused a potent dose-dependent induction of GLT-1 and GLAST mRNA and protein in these astrocytes. Importantly, the observed increase in glutamate transporters was found to have a functional effect, with significantly enhanced glutamate uptake in astrocytes treated with 100 or 1,000 uM PPF that was sensitive to dihydrokainate inhibition, suggesting it is GLT-1 mediated.
| Substance Class |
Chemical
Created
by
admin
on
Edited
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on
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| Record UNII |
5RTA398U4H
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| Record Status |
Validated (UNII)
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NCI_THESAURUS |
C1509
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WHO-VATC |
QC04AD90
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QN06BC02
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N06BC02
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C81919
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5RTA398U4H
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CHEMBL1079905
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100000081173
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PROPENTOFYLLINE
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m9197
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34644
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ACTIVE MOIETY |
