Zolpidem binding sites on the GABA(A) receptor in brain from human cirrhotic and non-cirrhotic alcoholics.
The displacement of [3H]flunitrazepam by unlabelled flunitrazepam or zolpidem was used to assess the affinity and density of sub-types of GABA(A) receptors in the superior frontal and primary motor cortices of ten alcoholic, seven alcoholic-cirrhotic and ten matched control cases. The binding was best fitted by a model with a single site for flunitrazepam, but two sites for zolpidem. Neither the patients' age nor the post-mortem interval were significantly correlated with the affinity or density of any of the binding sites. The affinity of all ligands did not differ either between cortical regions or across case groups. Hence, the density of each binding site was analyzed at constant affinity. The densities of flunitrazepam and high-affinity zolpidem binding sites were invariant across cortical regions and case groups. Low-affinity zolpidem binding sites were significantly more dense in the frontal than in the motor cortex of alcoholic cases irrespective of cirrhosis, whereas this regional difference was not significant in control cases.
Lewohl
J M
JM
Clinical Research Laboratory, Royal Brisbane Hospital Research Foundation, Bancroft Centre, Queensland, Australia.
Crane
D I
DI
Dodd
P R
PR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism; D011180:Postmortem Changes; D011725:Pyridines / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011963:Receptors, GABA-A / Q000378:metabolism*; D015854:Up-Regulation; D000077334:Zolpidem
D011725:Pyridines; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005445:Flunitrazepam; D000077334:Zolpidem