[123I]Iomazenil spect imaging demonstrates significant benzodiazepine receptor reserve in human and nonhuman primate brain

  title={[123I]Iomazenil spect imaging demonstrates significant benzodiazepine receptor reserve in human and nonhuman primate brain},
  author={Elzbieta H. Sybirska and John Seibyl and James Douglas Bremner and R. Michael Baldwin and Mohammed S. Al-Tikriti and Charles W. Bradberry and Robert Malison and Yolanda Zea‐Ponce and S. S. Zoghbi and Matthew J. During and A. W. Goddard and Steven W. Woods and Paul B. Hoffer and Dennis S. Charney and Robert B. Innis},

SPECT [I-123]iomazenil measurement of the benzodiazepine receptor in panic disorder

A proof-of-concept study using [11C]flumazenil PET to demonstrate that pagoclone is a partial agonist

The GABA-ergic system is central to many anxiety disorders and has therefore received much attention. Benzodiazepines are highly effective anxiolytics, leading to their widespread use clinically.

I-123 iomazenil SPECT in patients with mental disorders

The rapid washout of I-123 iomazenil from the brains of BZ (+) patients suggests that chronic administration of a clinical dose of Bz affects the binding of I -123 iosine to BZR on the brain.

GABAA receptor occupancy by subtype selective GABAAα2,3 modulators: PET studies in humans

High GABAA receptor occupancy by AZD7325 and AZD6280 could be reached without clear sedative effects and safety and tolerability was determined.

Tiagabine Increases [11C]flumazenil Binding in Cortical Brain Regions in Healthy Control Subjects

Preliminary evidence of the ability to measure in vivo, with PET, acute fluctuations in extracellular GABA levels is provided and the first in vivo documentation of a relationship between GABA neurotransmission and EEG γ-band power in humans is provided.

[11C]flumazenil Binding Is Increased in a Dose-Dependent Manner with Tiagabine-Induced Elevations in GABA Levels

It is demonstrated that the magnitude of increase in [11C]flumazenil binding observed with PET is directly correlated with tiagabine dose, and the ability to measure in vivo, with PET, acute shifts in extracellular GABA is demonstrated.

Benzodiazepine Receptor Antagonists

Flumazenil represents a promising tool for pharmacological investigations of the GABAergic system and for imaging of the benzodiazepine receptor, and as a neuronal marker in epilepsy and cerebral ischaemia.



SPECT Imaging of the benzodiazepine receptor: Autoradiographic comparison of receptor density and radioligand distribution

The ex vivo autoradiograms provided quantitative data from a realistic “biological phantom,” which may be used to assess the accuracy of image reconstruction and to investigate differences between the distribution of an intravenously administered tracer and that of its target in brain tissue.

SPECT imaging of the benzodiazepine receptor: feasibility of in vivo potency measurements from stepwise displacement curves.

In conclusion, stepwise displacement by agents administered following the injection of the radioligand 123I-Ro 16-0154 provided a reliable means of measuring the in vivo potencies of BZ receptor agents.

In vitro and in vivo evaluation of iodine-123-Ro 16-0154: a new imaging agent for SPECT investigations of benzodiazepine receptors.

The purified 123I-Ro 16-0154 was found to be stable in rat brain preparations and to be metabolized in rat liver preparations, and its pharmacologic properties were comparable to those of flumazenil.

Kinetics of [3H]flunitrazepam binding to membrane-bound benzodiazepine receptors.

The kinetics of [3H]flunitrazepam binding to synaptosomal (P2) membranes from rat cerebral cortex was studied and dissociation was faster before equilibrium than after equilibrium had been reached.

GABAergic modulation of benzodiazepine binding site sensitivity

GA can modulate the responsiveness of this BZ binding site since the addition of GABA to cortical membranes in vitro results in an increased affinity of the 3H-diazepam binding site for its ligand.

Stimulation of benzodiazepine receptor binding by gamma-aminobutyric acid.

  • M. KarobathG. Sperk
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1979
It is suggested that the described stimulation of benzodiazepine high-affinity binding is mediated by a receptor for GABA, as characterized by high-Affinity binding of GABA agonists.