EFFECTS OF A XANTHINE DERIVATIVE, PROPENTOFYLLINE, ON LOCAL CEREBRAL BLOOD-FLOW AND GLUCOSE-UTILIZATION IN THE RAT

The effects of the xanthine derivative propentofylline [3-methyl-1-(5' -oxohexyl)-7-propylxanthine] were measured on local cerebral blood flo w and glucose utilization in the rat using quantitative autoradiograph ic techniques. A dose of 0.5 mg/kg/min i.v. produced increases in loca l cerebral blood flow and minimal effects on glucose utilization in th e majority of cerebral structures measured. A higher dose of propentof ylline (1.5 mg/kg/min) produced an overall increase in local cerebral blood flow and a marked reduction in glucose utilization. Furthermore, propentofylline increased the average ratio of blood flow per unit gl ucose utilization and thus is capable of increasing cerebral blood flo w in excess of metabolic demand. While the mechanism of action of this compound has not been fully defined, it is possible that its cerebrov ascular and cerebral metabolic effects can at least partially be expla ined by a blockade of adenosine uptake. These actions of propentofylli ne on cerebral blood flow and metabolism may play a role in protecting neuronal tissue under hypoxic/ischemic conditions in the brain.