Radiosynthesis and Evaluation of 11C-Labeled Isoindolone-Based Positive Allosteric Modulators for Positron Emission Tomography Imaging of Metabotropic Glutamate Receptor 2.

The metabotropic glutamate receptor 2 (mGluR) has emerged as a potential therapeutic target for the treatment of various neurological diseases, prompting substantial interest in the development of mGluR-targeted drug candidates. As part of our medicinal chemistry program, we synthesized a series of isoindolone derivatives and assessed their potential as mGluR positive allosteric modulators (PAMs). Notably, AZ12559322 exhibited high affinity ( mGluR = 1.

Altered Serotonin 1B Receptor Binding After Escitalopram for Depression Is Correlated With Treatment Effect.

Background: Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively.

High Contrast PET Imaging of Subcortical and Allocortical Amyloid-β in Early Alzheimer's Disease Using [11C]AZD2184.

Background: Deposits of amyloid-β (Aβ) appear early in Alzheimer's disease (AD).

Objective: The aim of the present study was to compare the presence of cortical and subcortical Aβ in early AD using positron emission tomography (PET).

Methods: Eight cognitively unimpaired (CU) subjects, 8 with mild cognitive impairment (MCI) and 8 with mild AD were examined with PET and [11C]AZD2184.

PET Evaluation of the Novel F-18 Labeled Reversible Radioligand [F]GEH200449 for Detection of Monoamine Oxidase-B in the Non-Human Primate Brain.

Positron emission tomography (PET) using radioligands for the enzyme monoamine oxidase B (MAO-B) is increasingly applied as a marker for astrogliosis in neurodegenerative disorders. In the present study, a novel reversible fluorine-18 labeled MAO-B compound, [F]GEH200449, was evaluated as a PET radioligand in non-human primates. PET studies of [F]GEH200449 at baseline showed brain exposure (maximum concentration: 3.

CSF dopamine is elevated in first-episode psychosis and associates to symptom severity and cognitive performance.

Background: The hypothesis of dopamine dysfunction in psychosis has evolved since the mid-twentieth century. However, clinical support from biochemical analysis of the transmitter in patients is still missing. The present study assessed dopamine and related metabolites in the cerebrospinal fluid (CSF) of first-episode psychosis (FEP) subjects.