Benzodiazepine-GABAA receptors in idiopathic generalized epilepsy measured with [11C]flumazenil and positron emission tomography.
The neurochemical basis of absence seizures and the mechanism of their suppression by valproate (VPA) are uncertain. We used positron emission tomography (PET) to determine whether an abnormality of [11C]flumazenil binding to benzodiazepine (BZD)-GABAA receptors exists in patients with childhood and juvenile absence epilepsy and to examine the effects of VPA on [11C]flumazenil binding. The regional cerebral volume of distribution (Vd) of [11C]flumazenil in patients not treated with VPA was not different from that in normal controls; Vd was lower in patients treated with VPA, and the number of receptors available for binding was significantly reduced in such patients as compared with normal controls. There was no evidence of a primary abnormality of the BZD-GABAA receptor in childhood and juvenile absence epilepsy (CAE/JAE), but the data suggest that treatment with VPA is associated with a reduction in [11C]flumazenil binding that may be relevant to its mode of action in CAE/JAE.
Prevett
M C
MC
MRC Cyclotron Unit, Hammersmith Hospital, London, England.
Lammertsma
A A
AA
Brooks
D J
DJ
Bartenstein
P A
PA
Patsalos
P N
PN
Fish
D R
DR
Duncan
J S
JS
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004832:Epilepsy, Absence / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005442:Flumazenil / Q000378:metabolism*; D006801:Humans; D008297:Male; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use
D002250:Carbon Radioisotopes; D018079:Receptors, GABA; D005442:Flumazenil; D014635:Valproic Acid