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Propentofylline: a nucleoside transport inhibitor with neuroprotective effects in cerebral ischemia
F E Parkinson1, K A Rudolphi, B B Fredholm
1Department of Pharmacology and Therapeutics, Faculty of Medicine University of Manitoba, Winnipeg, Canada.
Abstract:
1. Adenosine is an endogenous neuroprotective agent; stimulation of A1 receptors decreases excitatory amino acid neurotransmission and stimulation of A2 receptors inhibits platelet and neutrophil activation and promotes vasodilation. 2. Post-ischemic administration of propentofylline (HWA 285) reduces neuronal damage in gerbils and improves glucose metabolism in all regions of brain in acute stroke patients. 3. Propentofylline inhibits the transport of adenosine into cultured cells and increases extracellular adenosine concentrations in ischemic brain. Thus, enhanced stimulation of adenosine receptors may account for some of the neuroprotective effects of this compound. 4. Propentofylline inhibits free radical production by cultivated microglia cells, stimulates nerve growth factor production and inhibits cAMP-phosphodiesterase activity. These effects may also be important for neuroprotection.