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Propentofylline: Glial Modulation, Neuroprotection, and Alleviation of Chronic Pain

  • Sarah Sweitzer
  • Joyce De LeoEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 200)

Abstract

Propentofylline is a unique methylxanthine with clear cyclic AMP, phosphodiesterase, and adenosine actions, including enhanced synaptic adenosine signaling. Both in vitro and in vivo studies have demonstrated profound neuroprotective, antiproliferative, and anti-inflammatory effects of propentofylline. Propentofylline has shown efficacy in preclinical models of stroke, opioid tolerance, and acute and chronic pain. Clinically, propentofylline has shown efficacy in degenerative and vascular dementia, and as a potential adjuvant treatment for schizophrenia and multiple sclerosis. 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. This chapter reviews the literature that supports a myriad of protective actions of this small molecule and implicates propentofylline as a potential therapeutic for the treatment of chronic pain. From these studies, we propose a CNS multipartite synaptic action of propentofylline that includes modulation of pre- and postsynaptic neurons, astrocytes, and microglia in the treatment of chronic pain syndromes, including, but not limited to, neuropathic pain.

Keywords

Astrocytes Cytokines Glia Microglia Neuropathic pain Opioids Tolerance 

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Copyright information

© Springer Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Pharmacology, Physiology and NeuroscienceUniversity of South Carolina, USC School of MedicineColumbiaUSA
  2. 2.Department of Pharmacology and ToxicologyDartmouth Medical SchoolHanoverUSA

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