Propentofylline (HWA 285), a neuroprotective glial cell modulator: Pharmacologic profile

Abstract

Propentofylline is a neuroprotective glial cell modulator with multiple functional effects (Fig. 2). Propentofylline inhibits cytotoxic functions of activated microglia and also modulates astrocyte functions by stimulating NGF synthesis/secretion. It improves learning and memory in experimental models of dementia and enhances hippocampal LTP. In experimental models of global and focal brain ischemia, the drug exerts tissue-saving neuroprotective effects. Propentofylline's molecular mechanism of action is the concerted inhibition of Na+-independent adenosine transporters and cyclic nucleotides PDEs, I, II, and IV. The drug thereby reinforces the multiple cellular actions of the endogenous modulator adenosine and the cellular second messengers cAMP and cGMP. Preclinical and clinical studies indicate that propentofylline has the potential to become a safe and efficacious drug for the treatment of both VaD and AD.