Toward Multidisciplinary Tools for Complex Clinical Psychopharmacology Cases: A Qualitative Study with French Healthcare Professionals.

Purpose: Psychopharmacology prescriptions are complex, partly due to the complexity of the relationship between diagnosis and its etiology, as well as the iatrogenic impact on symptomatology. Many multidisciplinary tools exist to optimize their management and improve evidence-based practice. However, their multidisciplinary integration seems to be a challenge.

Serotonin 5-HT receptor biased agonists: The challenge of translating an innovative neuropharmacological concept into therapeutics.

Serotonin 5-HT receptor agonists are prime candidates for CNS drug discovery due to their involvement physiological and pathological processes relevant to neurology and psychiatry. However, the lack of target specificity of many previously characterized agonists has long been a barrier to pharmacological and therapeutic progress. Some of the obstacles may be overcome through the recent concept of biased agonism, which has attracted considerable attention to the development of novel chemical entities at 5-HT, and particularly 5-HT receptors, by specifically targeting intracellular signalling pathways that may themselves be linked to specific brain regions and therapeutic indications.

[F]RS-127445 radiosynthesis and evaluation as a 5-HT receptor PET radiotracer in rat brain.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter involved in many physiological and pathological mechanisms through its numerous receptors. Among these, the 5-HT receptor is known to play a key role in multiple brain disorders but remains poorly understood. Positron emission tomography (PET) can contribute to a better understanding of pathophysiological mechanisms regulated by the 5-HT receptor.

Toward Functional PET Imaging of the Spinal Cord.

At present, spinal cord imaging primarily uses magnetic resonance imaging (MRI) or computed tomography (CT), but the greater sensitivity of positron emission tomography (PET) techniques and the development of new radiotracers are paving the way for a new approach. The substantial rise in publications on PET radiotracers for spinal cord exploration indicates a growing interest in the functional and molecular imaging of this organ. The present review aimed to provide an overview of the various radiotracers used in this indication, in preclinical and clinical settings.

Preclinical investigation of the effect of stress on the binding of [F]F13640, a 5-HT radiopharmaceutical.

Background: [F]F13640 is a new PET radiopharmaceutical for brain molecular imaging of serotonin 5-HT receptors. Since we intend to use this radiopharmaceutical in psychiatric studies, it is crucial to establish possible sensitivity modification of 5-HT receptors availability during an acute stress exposure. In this study, we first assessed the cerebrometabolic effects of a new animal model of stress with [F]FDG and then proceeded to test for effects of this model on the cerebral binding of [F]F13640, a 5-HT receptors PET radiopharmaceutical.

NMDA antagonist agents for the treatment of symptoms in autism spectrum disorder: a systematic review and meta-analysis.

Aims: This systematic review and meta-analysis aimed to assess the efficacy of NMDA antagonists in ASD (Autism Spectrum Disorder) on the core (communication and social interaction, repetitive behavior) and associated symptoms (irritability) of ASD, as well as their safety.

Methods: PubMed, CENTRAL, CINHAL, EMBASE, and PsycINFO databases were searched until November 2023. Two authors independently selected the studies and extracted data.

Pharmacodynamic, pharmacokinetic and rat brain receptor occupancy profile of NLX-112, a highly selective 5-HT receptor biased agonist.

NLX-112 (i.e., F13640, befiradol) exhibits nanomolar affinity, exceptional selectivity and full agonist efficacy at serotonin 5-HT receptors.

Identification of factors associated with hospitalization in an outpatient population with mental health conditions: a case-control study.

Introduction: Addressing relevant determinants for preserved person-centered rehabilitation in mental health is still a major challenge. Little research focuses on factors associated with psychiatric hospitalization in exclusive outpatient settings. Some variables have been identified, but evidence across studies is inconsistent.

SB-258585 reduces food motivation while blocking 5-HT receptors in the non-human primate striatum.

The interest in new 5-HT₆ agents stems from their ability to modulate cognition processing, food motivation and anxiety-like behaviors. While these findings come primarily from rodent studies, no studies on primates have been published. Furthermore, our understanding of where and how they act in the brain remains limited.

A revisited version of the disputatio for pharmacological training: An educational study.

Objective: The disputatio is a pedagogical method existing since the Middle-Ages where students had to debate about a question asked by a "master", exercising their thinking and oratory skills. To move away from traditional vertical teaching methods, the disputatio has been revived by pharmacologists. Thus, for almost three successive years, several groups of young French pharmacologists and therapists confronted their ideas concerning a medical question at a therapeutic impasse.

Recent applications of positron emission tomographic (PET) imaging in psychiatric drug discovery.

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

3D-printed dual holder system for simultaneous rat PET scanning: design and influence on quantification.

Background: The low throughout of small animal positron emission tomography (PET) images acquisitions represents a substantial limitation. The aims of this study were (i) to design a low-cost support for simultaneous dynamic PET scanning of two lying rats and (ii) to study its impact on brain image quantification.

Results: Accuracy of concentration measurement was 5.

Multimodal imaging study of the 5-HT receptor biased agonist, NLX-112, in a model of L-DOPA-induced dyskinesia.

Introduction: The leading treatment for motor signs of Parkinson's disease is L-DOPA, but, upon extended use, it can lead to levodopa-induced dyskinesia (LID). Serotonergic neurons are involved in LID etiology and previous pre-clinical studies have shown that NLX-112, a 5-HT biased agonist, has robust antidyskinetic effects. Here, we investigated its effects in hemiparkinsonian (HPK) rats with a unilateral nigrostriatal 6-OHDA lesion.

Single subanesthetic dose of ketamine produces delayed impact on brain [F]FDG PET imaging and metabolic connectivity in rats.

Introduction: Ketamine, a glutamate NMDA receptor antagonist, is suggested to act very rapidly and durably on the depressive symptoms including treatment-resistant patients but its mechanisms of action remain unclear. There is a requirement for non-invasive biomarkers, such as imaging techniques, which hold promise in monitoring and elucidating its therapeutic impact.

Methods: We explored the glucose metabolism with [F]FDG positron emission tomography (PET) in ten male rats in a longitudinal study designed to compare imaging patterns immediately after acute subanaesthetic ketamine injection (i.

Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic.

The immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, multiple pieces of evidence now support the view that B cells are essential players in multiple sclerosis pathogenic processes. High-efficacy disease-modifying therapies that target the immune system have emerged over the past two decades.

Positron Emission Tomography for the Discovery of New Drugs in Psychiatry.

The arsenal of drugs for psychiatry has been difficult to renew for several decades. Many failures in therapeutic trials can be explained by poorly evaluated pharmacological properties, in terms of brain passage, target binding, and functional modulation. Positron emission tomography can provide pharmacokinetic and pharmacodynamic data that will help to better select candidate molecules for larger-scale clinical trials.

[F]F13640: a selective agonist PET radiopharmaceutical for imaging functional 5-HT receptors in humans.

Purpose: F13640 (a.k.a.

Pharmaco-fUS in cognitive impairment: Lessons from a preclinical model.

Background: There is an urgent need to understand and reverse cognitive impairment. The lack of appropriate animal models combined with the limited knowledge of pathophysiological mechanisms makes the development of new cognition-enhancing drugs complex. Scopolamine is a pharmacologic agent which impairs cognition and functional imaging in a wide range of animal species, similarly to what is seen in cognitive impairment in humans.

Impaired Local and Long-Range Brain Connectivity and Visual Response in a Genetic Rat Model of Hyperactivity Revealed by Functional Ultrasound.

Attention-Deficit hyperactivity disorder (ADHD) is a central nervous system (CNS) disorder frequently associated with other psychiatric disorders. Pathophysiology processes at stake in ADHD are still under investigation and interestingly neuroimaging data points to modulated brain connectivity in patients. The genetic spontaneously hypertensive rat (SHR) model has been widely used to study pathophysiological underpinnings of ADHD and resting-state brain connectivity using functional magnetic resonance imaging.

PET Metabolic Imaging of Time-Dependent Reorganization of Olfactory Cued Fear Memory Networks in Rats.

Memory consolidation involves reorganization at both the synaptic and system levels. The latter involves gradual reorganization of the brain regions that support memory and has been mostly highlighted using hippocampal-dependent tasks. The standard memory consolidation model posits that the hippocampus becomes gradually less important over time in favor of neocortical regions.

Comparative diagnosis interest of NfL and pNfH in CSF and plasma in a context of FTD-ALS spectrum.

Objective: The 'Frontotemporal dementia-Amyotrophic lateral sclerosis Spectrum' (FAS) encompasses different phenotypes, including cognitive disorders (frontotemporal dementia, FTD) and/or motor impairments (amyotrophic lateral sclerosis, ALS). The aim of this study was to apprehend the specific uses of neurofilaments light chain (NfL) and phosphorylated neurofilaments heavy chain (pNfH) in a context of FAS.

Methods: First, NfL and pNfH were measured in 39 paired cerebrospinal fluid (CSF) and plasma samples of FAS and primary psychiatric disorders (PPD) patients, considered as controls.