Central benzodiazepine receptor occupancy by zolpidem in the human brain as assessed by positron emission tomography

• Published in: European journal of pharmacology Vol. 295; no. 1; pp. 35 - 44
• Main Authors: Abadie, Pascale, Rioux, Patrice, Scatton, Bernard, Zarifian, Edouard, Barré, Louisa, Patat, Alain, Baron, Jean-Claude
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04-01-1996; Elsevier
• Subjects: [ 11C]Flumazenil; Adult; Benzodiazepine receptor, central; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Flumazenil - pharmacology; Humans; Hypnotics. Sedatives; Imidazopyridine; Male; Medical sciences; Neuropharmacology; PET (positron emission tomography); Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Pyridines - pharmacology; Radioligand Assay; Receptors, GABA-A - drug effects; Receptors, GABA-A - metabolism; Time Factors; Tissue Distribution; Tomography, Emission-Computed; Zolpidem; [ 11C]Flumazenil; Imidazopyridine; Benzodiazepine receptor, central; PET (positron emission tomography); Human; Biological fixation; Central nervous system; Oral administration; Hypnotic; Benzodiazepine receptor; Localization; Normal; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(95)00633-8

The central benzodiazepine receptor occupancy by zolpidem in man is unknown. The present study used positron emission tomography (PET) and [
11C]flumazenil to assess in five healthy volunteers, central benzodiazepine receptor occupancy in brain regions with high receptor densities 1 h following an acute oral administration of twice the usual hypnotic dose of zolpidem (20 mg). Receptor occupancy was measured in five discrete structures (middle frontal gyrus, middle temporal gyrus, posterior occipital cortex, lateral parietal cortex, and cerebellar cortex) and in a large neocortical area as the fractional change in the [
11C]flumazenil bound/free ratio for the interval 15–40 min post-administration of the radiotracer. The free-radioligand concentration was estimated from the pons, a reference structure virtually devoid of central benzodiazepine receptor. With individual pons values, mean occupancy was about 21% but with spurious inter-subject variability. With pons values averaged across the five subjects and separately for control and treated condition, the occupancy was (mean ± S.D.) 27 ± 11% for the whole neocortex, and ranged from 26 to 29% in the five discrete structures (
P < 0.01). By showing hypnotic effect at moderate occupancies, this study directly provides evidence for the full-agonist properties of zolpidem in human.