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.