The effects of an alpha-2 adrenergic agonist, guanfacine, on rCBF in humancortex in normal controls and subjects with focal epilepsy

Alpha-2 noradrenergic agonists may have wide applicability in the treatment of pre-frontal cortex deficits in primates and behavioral dysfunction in m an. We have undertaken this study to determine the effect on an alpha-2 ago nist, guanfacine, on regional cerebral blood flow (rCBF) in humans. Three s ubject groups were evaluated: normal controls, subjects with frontal lobe e pilepsy (FLE), and subjects with temporal lobe epilepsy (TLE). All underwen t a number of PET scans using O-15-water, with half before and half after a single dose of guanfacine in controls and subjects with TLE. Smaller areas of decrease in rCBF were seen in the posterior temporal-occipital cortex. In the FLE group a decrease in rCBF was seen in the dorsal prefrontal corte x on the epileptogenic side with only small increases seen in the mid- to a nterior temporal perisylvian areas. The ability of alpha-2 agonists to enha nce performance of tasks reliant on prefrontal cortex, without improving ta sks believed to rely on intact temporal-hippocampal function, may be explai ned by these results. Epileptogenic zones appear to create both direct and indirect changes in patterns of drug response. Further studies on the cogni tive properties of these agents in humans should be encouraged. (C) 2000 Am erican College of Neuropsychopharmacology. Published by Elsevier Science In c. All rights reserved.