Autism spectrum disorder (ASD) is an early-onset disorder with a prevalence of 1% among children and reported disability-adjusted life years of 4.31 million. Irritability is a challenging behavior associated with ASD, for which medication development has lagged. More specifically, pharmacotherapy effectiveness may be limited against high adverse effects (considering side effect profiles and patient medication sensitivity); thus, the possible benefits of pharmacological interventions must be balanced against potential adverse events in each patient.

AREAS COVERED:

After reviewing the neuropathophysiology of ASD-associated irritability, the benefits and tolerability of emerging medications in its treatment based on randomized controlled trials were detailed in light of mechanisms and targets of action.

EXPERT OPINION:

Succeeding risperidone and aripiprazole, monotherapy with memantine may be beneficial. In addition, N-acetylcysteine, galantamine, sulforaphane, celecoxib, palmitoylethanolamide, pentoxifylline, simvastatin, minocycline, amantadine, pregnenolone, prednisolone, riluzole, propentofylline, pioglitazone, and topiramate, all adjunct to risperidone, and clonidine and methylphenidate outperformed placebo. These effects were through glutamatergic, γ-aminobutyric acidergic, inflammatory, oxidative, cholinergic, dopaminergic, and serotonergic systems. All medications were reported to be safe and tolerable. Considering sample size, follow-up, and effect size, further studies are necessary. Along with drug development, repositioning and combining existing drugs supported by the mechanism of action is recommended.

07 Jun 2023·Biomedicines

Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem.

Article

Author: Bondan, Eduardo F ; Pereira, Álvaro A F ; Baliellas, Deborah E M ; Guariroba, Maísa ; Martins, Maria F ; Poppe, Sandra C ; Barros, Marcelo P ; Vardaris, Cristina V

Propentofylline (PROP) is a methylated xanthine compound that diminishes the activation of microglial cells and astrocytes, which are neuronal cells strongly associated with many neurodegenerative diseases. Based on previously observed remyelination and neuroprotective effects, PROP has also been proposed to increment antioxidant defenses and to prevent oxidative damage in neural tissues. Since most neurodegenerative processes have free radicals as molecular pathological agents, the aim of this study was to evaluate the antioxidant effects of 12.5 mg·kg^-1·day^-1 PROP in plasma and the brainstem of Wistar rats exposed to the gliotoxic agent 0.1% ethidium bromide (EB) for 7-31 days. The bulk of the data here demonstrates that, after 7 days of EB treatment, TBARS levels were 2-fold higher in the rat CNS than in control, reaching a maximum of 2.4-fold within 15 days. After 31 days of EB treatment, lipoperoxidation in CNS was still 65% higher than that in the control. Clearly, PROP treatment limited the progression of lipoperoxidation in EB-oxidized CNS: it was, for example, 76% lower than in the EB-treated group after 15 days. Most of these effects were associated with PROP-induced activity of glutathione reductase in the brainstem: the EB + PROP group showed 59% higher GR activity than that of the EB or control groups within 7 days. In summary, aligning with previous studies from our group and with literature about MTXs, we observed that propentofylline (PROP) improved the thiol-based antioxidant defenses in the rat brainstem by the induction of the enzymatic activity of glutathione reductase (GR), which diminished lipid oxidation progression and rebalanced the redox status in the CNS.

01 Jan 2021·The Veterinary recordQ3 · AGRICULTURAL & FORESTRY SCIENCE

Cognitive Dysfunction in Cats: Update on Neuropathological and Behavioural Changes Plus Clinical Management

Q3 · AGRICULTURAL & FORESTRY SCIENCE

Review

Author: Sordo, Lorena ; Gunn‐Moore, Danièlle A.

Abstract:

Cognitive dysfunction syndrome (CDS) is an established condition in cats that shares many similarities with human Alzheimer's disease (AD), where cognitive decline ultimately results in dementia. Cats with CDS display behavioural abnormalities, including excessive Vocalisation, altered Interaction with owners (increased affection/attention), altered Sleep‐wake cycles, House‐soiling, Disorientation (spatial and/or temporal), alterations in Activity, Anxiety, and/or Learning/memory deficits (i.e., VISHDAAL). These cats develop neuropathologies, such as accumulation of β‐amyloid and hyperphosphorylated tau deposits. Because of its similarities to those in the brains of people with cognitive impairment and AD, the domestic cat could be a natural model for human dementia studies. It is important to diagnose CDS promptly in cats, ruling out other causes for these behavioural changes, to provide effective management. Interventions include environmental enrichment (e.g., easy access to key resources, calming pheromones), dietary supplementations (e.g., Senilife, Aktivait for cats, SAMe), specific diets (e.g., containing antioxidants, medium‐chain triglycerides) and, potentially, medication (e.g., selegiline or propentofylline). This article reviews the literature about CDS in cats, its causes, neuropathology, clinical signs, diagnosis and potential management options. By doing so, it furthers our understanding of this condition and allows improved health, welfare and quality of life of affected cats.

News (Medical) associated with Propentofylline

08 Sep 2022

·www.prnewswire.com

Entrepreneurial Accelerator Program (EAP) Portfolio Company receives $400,000 Research Grant from The National Cancer Institute to study a repurposed drug in treatment of Glioblastoma

SHREVEPORT, La., Sept. 8, 2022 /PRNewswire/ -- Entrepreneurial Accelerator Program (EAP) portfolio company Oleolive, Inc. has been awarded a Small Business Technology Transfer (STTR) Phase 1 $400,000 research grant from the National Cancer Institute for "Chemosensitization of Glioblastoma by Propentofylline." Drs. Nhan Tran and Joseph Loftus, investigators at Mayo Clinic and experts in Glioblastoma Multiforme (GBM), collaborated with Oleolive on the proposal. Propentofylline (PPF) was originally tested in multiple clinical trials for Alzheimer's disease but, although shown to be safe and effective, was not brought to the commercial market. PPF is considered a repurposed drug, defined as a drug developed for one indication and repositioned to treat another, in this case GBM. Repurposed drugs require less money and time for development and overall costs much less compared to research and development of new drugs. GBM is a brain cancer with no effective therapeutics that claims the lives of over 15,000 Americans each year. GBM has poor clinical outcomes due to therapy-resistant tumor cells leading to recurrence; therefore, therapeutic strategies that enhance tumor cell chemosensitivity are essential for improved patient outcomes. This project will evaluate if PPF increases sensitization of GBM tumor cells to chemotherapy. This research could lead to a therapeutic strategy to extend survival for GBM patients beyond the current average of 1.25 years. About Oleolive, Inc . Oleolive, Inc. is a preclinical private biotechnology company founded in 2017, located in Shreveport, Louisiana. The company is developing therapeutics to treat a variety of human indications, including brain cancer, Alzheimer's disease, fibrosis, and traumatic blood loss in austere environments. The company has received more than $5M in STTRs and small business innovation research (SBIR) grant awards from multiple funding sources including the National Institute on Aging, the National Cancer Institute, the National Heart, Lung, and Blood Institute and the Department of Defense. Oleolive also manufactures the dietary ingredient Oligen which contains compounds from Extra Virgin Olive Oil that promote healthy aging. To learn more about Oleolive, Inc. please visit our website , or contact [email protected] with inquiries. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R41CA268286. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. SOURCE Entrepreneurial Accelerator Program

Small molecular drugCollaborate

100 Deals associated with Propentofylline

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KEGG	Wiki	ATC	Drug Bank
D01630	Propentofylline	N06BC02	DB06479

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Cerebrovascular Disorders	KR	Sanofi	30 Oct 1997

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	NDA/BLA	EU	Hoechst Pakistan Ltd.	-
Alzheimer Disease	NDA/BLA	CA	Hoechst Pakistan Ltd.	-
Dementia, Vascular	NDA/BLA	EU	Hoechst Pakistan Ltd.	-
Dementia, Vascular	NDA/BLA	CA	Hoechst Pakistan Ltd.	-
Glioblastoma	Preclinical	US	Oleolive, Inc.Startup	17 Nov 2022

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