Recent applications of positron emission tomographic (PET) imaging in psychiatric drug discovery DOI
Luc Zimmer

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 19(2), P. 161 - 172

Published: Nov. 10, 2023

Introduction Psychiatry is one of the medical disciplines that suffers most from a lack innovation in its therapeutic arsenal. Many failures drug candidate trials can be explained by pharmacological properties have been poorly assessed upstream, terms brain passage, target binding and clinical outcomes. Positron emission tomography provide pharmacokinetic pharmacodynamic data to help select candidate-molecules for further trials.

Language: Английский

Small molecule probes for the specific imaging of monoamine oxidase A and monoamine oxidase B DOI Creative Commons
Yi Fang, Zhengping Chen, Min Yang

et al.

iRadiology, Journal Year: 2024, Volume and Issue: 2(2), P. 191 - 215

Published: March 27, 2024

Abstract Monoamine oxidases (MAOs) are a class of flavin enzymes that mainly present in the outer membrane mitochondria and play crucial role maintaining homeostasis monoamine neurotransmitters central nervous system. Furthermore, expression MAOs is associated with functions peripheral organs. Dysfunction relevant variety diseases such as neurodegenerative diseases, heart failure, metabolic disorders, cancers. have two isoenzymes, namely, oxidase A (MAO‐A) B (MAO‐B). Therefore, development reliable specific methods to detect these isoenzymes great significance for in‐depth understanding their biological systems, further promoting clinical diagnosis treatment MAO‐related diseases. This review focuses on advances small molecular probes imaging MAO‐A MAO‐B, including radiolabeled probes, fluorescent 19 F magnetic resonance probe. In addition, applications detecting MAO levels cells, tissues, animal models, patients described. Finally, challenges perspectives developing novel also highlighted.

Language: Английский

Citations

3
Validation of a pharmacological imaging challenge using 11C-buprenorphine and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography to study the effects of buprenorphine to the rat brain DOI Creative Commons

Amélie Soyer,

Sarah Leterrier, Louise Breuil

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: May 10, 2023

Buprenorphine mainly acts as an agonist of mu-opioid receptors (mu-OR). High dose buprenorphine does not cause respiratory depression and can be safely administered to elicit typical opioid effects explore pharmacodynamics. Acute buprenorphine, associated with functional quantitative neuroimaging, may therefore provide a fully translational pharmacological challenge the variability response opioids in vivo. We hypothesized that CNS acute could monitored through changes regional brain glucose metabolism, assessed using 18F-FDG microPET rats.First, level receptor occupancy single (0.1 mg/kg, s.c) was investigated blocking experiments 11C-buprenorphine PET imaging. Behavioral study elevated plus-maze test (EPM) performed assess impact selected on anxiety also locomotor activity. Then, imaging 30 min after injection unlabeled vs. saline. Two different acquisition paradigms were compared: (i) injected i.v. under anesthesia (ii) i.p. awake animals limit anesthesia.The blocked binding regions, suggesting complete occupancy. This had no significant behavioral tests used, regardless anesthetized/awake handling paradigm. In anesthetized rats, decreased uptake most regions except cerebellum which used normalization region. treatment significantly normalized thalamus, striatum midbrain (p < 0.05), where highest. The paradigm did improve sensitivity metabolism reliably estimated.Buprenorphine combined isoflurane rats provides simple investigate full by this partial mu-OR agonist. Sensitivity method improved animals. strategy useful de desensitization tolerance

Language: Английский

Citations

4
Structure-Affinity-Pharmacokinetics Relationships of Novel 18F-Labeled 1,4-Diazepane Derivatives for Orexin 1 Receptor Imaging DOI

Yui Ishizaka,

Hiroyuki Watanabe,

Masahiro Ono

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

The orexin 1 receptor (OX1R) has been suggested to be involved in the reward and autonomic nervous systems. Positron emission tomography (PET) of OX1R contributes elucidating its role developing new drugs. However, there are no useful PET probes for vivo imaging OX1R. Here, we newly designed synthesized

Language: Английский

Citations

0
Neuroreceptor Mapping in 2024 DOI
Ramya Tokala, Jacob M. Hooker

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Neuroreceptor mapping provides insights into neurotransmitter changes and receptor dynamics that improve the understanding of brain functions. This Viewpoint highlights advancements in development novel radiotracers (imaging tools) quantification based on presentations from

Language: Английский

Citations

0
Recent applications of positron emission tomographic (PET) imaging in psychiatric drug discovery DOI
Luc Zimmer

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 19(2), P. 161 - 172

Published: Nov. 10, 2023

Introduction Psychiatry is one of the medical disciplines that suffers most from a lack innovation in its therapeutic arsenal. Many failures drug candidate trials can be explained by pharmacological properties have been poorly assessed upstream, terms brain passage, target binding and clinical outcomes. Positron emission tomography provide pharmacokinetic pharmacodynamic data to help select candidate-molecules for further trials.

Language: Английский

Citations

1