Presentation

Confirmed speakers

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• Anne Andrews, University of California, Los Angeles - USA

  

  Anne Andrews

  University of California, Los Angeles

  Address: Neuroscience Research Building, 635 Charles E. Young Dr S, Box 957332
  Los Angeles, CA 90095-7332 - USA

   Email: aandrews@mednet.ucla.edu

  Anne Andrews is Professor of Psychiatry & Biobehavioral Sciences, Chemistry & Biochemistry, and Bioengineering at UCLA. She received her B.S. from the Pennsylvania State University and Ph.D. from the American University. She was a predoctoral, postdoctoral, and senior staff fellow at the National Institute of Mental Health. Andrews received an NIH Director’s Transformative Research Award, an IUPAC Distinguished Women in Chemistry Award, and an ACS Award in Electrochemistry, among others. Andrews advances basic and translational brain research. Her interdisciplinary team studies how neurotransmitters, including serotonin, encode emotionally salient information related to anxiety and stress responses. Andrews also develops wearable sensors to advance personalized medicine and improve health and wellness.

  Monitoring serotonin signaling: A journey in time and space

  We aim to understand how serotonin encodes information related to anxiety and stress. Throughout our research, we have developed and improved neuroanalytical methods to monitor serotonin levels in vivo with high temporal, spatial, and chemical resolution. Building on the pioneering work of Ralph Adams, we used electrochemical detection of serotonin to enhance fast microdialysis sampling combined with online HPLC. To directly sample the brain's extracellular signaling space, we developed rapid-pulse voltammetry paired with machine learning for multiplexed measurements of serotonin and dopamine. In addition to electrochemistry, we created electronic biosensors based on DNA aptamers for molecular recognition, coupled with field-effect transistors for electronic signal transduction. These sensors extend detection to non-electrochemically active neurotransmitters and hormones, allowing for implantable and wearable monitoring. Using high-resolution monitoring, we investigated the transgenerational impact of stress on anxiety-related behavior in adult mouse offspring and are working toward wearable, multiplexed biomarker measurements to provide personalized insights into human stress responses.

• Rita Bardoni , University of Modena and Reggio Emilia - IT

  

  Rita Bardoni

  University of Modena and Reggio Emilia

  Address:  Via Campi, 287 41125 Modena, Italy

   Email: rita.bardoni@unimore.it

  Rita Bardoni is an Associate Professor of Physiology at the University of Modena and Reggio Emilia. Her research focuses on the cellular and synaptic mechanisms underlying somatosensory transmission in the spinal cord dorsal horn. Using primarily electrophysiological approaches in in vitro spinal cord preparations, Dr. Bardoni has characterized the functional properties of identified dorsal horn neuronal populations and examined the role of specific synaptic receptors in the modulation of pain and itch signalling. More recently, her work has concentrated on the impact of serotonergic receptor activation on dorsal horn circuit activity, with particular emphasis on 5-HT1 and 5-HT7 receptors.

  5-HT7 receptor–mediated modulation of identified neuronal circuits in the superficial dorsal horn of the spinal cord

  5-HT7 receptors are abundantly expressed in the dorsal horn of the spinal cord, in both neuronal and glial populations. Their expression is predominantly associated with inhibitory GABAergic and glycinergic interneurons. Consistent with this distribution, behavioral studies indicate that spinal 5-HT7 receptors exert a primarily antinociceptive effect in both inflammatory and neuropathic pain models. Using an in vitro mouse spinal cord slice preparation, we showed that activation of 5-HT7 receptors by the selective agonist LP-211 modulates inhibitory synaptic transmission in laminae I–II of the dorsal horn, key regions for nociceptive processing. Specifically, LP-211 increased GABA and glycine release and enhanced the excitability of tonic-firing neurons, which are largely inhibitory interneurons. Optogenetic experiments further demonstrated that 5-HT7 receptor activation potentiates both spontaneous and light-evoked inhibitory synaptic transmission. This potentiation was mainly observed in excitatory interneurons, where inhibitory inputs were predominantly glycinergic. Consistently, preliminary data obtained with the 5-HT7 biased agonist serodolin revealed an increase in spontaneous inhibitory synaptic currents in excitatory interneurons.
  Overall, our results show that activation of 5-HT7 receptors strengthens inhibitory control over dorsal horn nociceptive interneurons, providing mechanistic support for the antinociceptive role of these receptors at the spinal level.

• Monika Bijata, Nencki Institute of Experimental Biology PAS - PL

  

  Monika Bijata

  Nencki Institute of Experimental Biology PAS

  Address:  Pasteur 3, 02-093 Warsaw - Poland

   Email: m.bijata@nencki.edu.pl

  Dr hab. Monika Bijata is a neuroscientist at the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw. Her research focuses on molecular and structural mechanisms of synaptic plasticity in neuropsychiatric disorders. She investigates how serotonin signaling, particularly via the 5-HT7 receptor, influences brain function under stress. Through a combination of behavioral, biochemical, imaging, and electrophysiological methods, she identified a novel signaling pathway linking 5-HT7 receptor activation with matrix metalloproteinase-9 (MMP-9) activity in the hippocampus. This pathway plays a key role in dendritic spine remodeling and the emergence of depressive-like behaviors, offering new insight into antidepressant mechanisms and potential therapeutic targets.

  5-HT7 receptor as a regulator of synaptic plasticity and molecular driver of depressive-like behaviors   

  Serotonergic signaling plays a fundamental role in regulating synaptic plasticity and emotional behavior. Our work synthesizes molecular and behavioral evidence identifying the 5-HT7 receptor (5-HT7R) as a critical modulator of hippocampal plasticity and a driver of depressive-like behaviors. We show that activation of 5-HT7R induces changes in synaptic structure. Acute and chronic 5-HT7R activation produce distinct synaptic and behavioral effects, with sustained receptor stimulation promoting maladaptive plasticity associated with depressive-like phenotypes in animal models. At the molecular level, these effects are mediated by a downstream signaling cascade involving matrix metalloproteinase-9 (MMP-9), which translates 5-HT7R activity into structural remodeling of dendritic spines and changes in synaptic efficacy. Importantly, the functional outcome of 5-HT7R signaling is further shaped by post-translational regulation, including receptor palmitoylation, which modulates constitutive receptor activity and downstream signaling and is disrupted under chronic stress conditions. It is associated with increased hippocampal MMP-9 activity, a finding mirrored in post mortem brain samples from individuals with depression. Together, these data position the 5-HT7R as a central molecular switch integrating serotonergic signaling, stress-dependent regulatory mechanisms, and synaptic remodeling underlying mood-related behaviors.

• Sylvie Claeysen , Institute of Functional Genomics (IGF) / INSERM, CNRS, Montpellier University - FR

  

  Sylvie Claeysen

  Institute of Functional Genomics (IGF) / INSERM, CNRS, University of Montpellier 

  Address:  141 rue de la Cardonille 34094 Montpellier cedex 5

   Email: sylvie.claeysen@igf.cnrs.fr

  Sylvie Claeysen is an Inserm researcher based at the Institute of Functional Genomics in Montpellier. She specialises in neuropharmacology, serotonin receptors and neurodegenerative diseases. Working with a network of clinicians, chemists and biotechnology companies, she proposes innovative strategies for treating Alzheimer's disease (multi-target drugs, biomarkers). A member of the Scientific Council of France Alzheimer (2015-2023) and of Inserm's Microbiota programme (2016-2025), she is currently a partner in the PREANALYTICS project of the national programme ‘Food Systems, Microbiomes and Health’ and co-leader of the MICMALZ clinical study. In this context, she is exploring the potential of gut microbiota modulation as a new therapeutic and preventive approach to Alzheimer's disease.

  Serotonin and the gut-brain axis  

  The gut microbiota plays a key role in human health and is capable of affecting brain function via the gut-brain axis. Serotonin plays a crucial role in this axis, acting as a signalling molecule that links gastrointestinal function with emotional and cognitive processes. Around 90% of the body’s serotonin is produced in the gut, where it regulates motility, secretion and sensory signalling. This peripheral serotonin interacts with the enteric nervous system and communicates with the central nervous system via neural pathways, particularly the vagus nerve, as well as through immune and endocrine routes. Disorders such as irritable bowel syndrome, anxiety, and depression are associated with alterations in serotonin signalling, highlighting its dual influence on gut and brain health. Understanding the integrative role of serotonin offers insight into novel therapeutic approaches that target gut-brain communication.

• Pascale Crépieux, Physiology of Reproduction and Behaviour (PRC) / Centre INRAE Val de Loire, CNRS, University of Tours, IFCE - FR

  

  Pascale Crépieux

  Physiology of Reproduction and Behaviour (PRC) / Centre INRAE Val de Loire, CNRS, University of Tours, IFCE

  Address:  Centre INRAE Val de Loire, 37380 Nouzilly, France

   Email: pascale.crepieux@inrae.fr

  Dr Pascale Crépieux is a CNRS research director at the Laboratory of Physiology of Reproduction and Behaviors in Nouzilly, France. She obtained her PhD in Molecular Oncology at the Pasteur Institute, France, then spent 3 years at McGill University, Canada, as a post-doc. Her research has revealed a developmental regulation of signalling processes during gonadal post-natal development, and have highlighted the importance of translational regulations in the trophic role of FSH in these cells. She is now exploring new approaches based on intracellular VHH, to interfere with the FSHR-mediated signalling and clarify the relationships between the FSHR structure and its activity. 

  Targeting FSHR and LHR with intracellular antibodies for structure-activity studies  

  Intracellular variable fragments of camelid heavy chain antibodies (intra-VHHs or nanobodies) have been successfully used as chaperones to resolve the 3D structure of active G protein-coupled receptors (GPCRs) bound to transducing proteins. They also provide insights into the relationships between receptor conformational states and signaling activity. So far, this property has been mainly examined for GPCRs binding peptide ligands. Using a next-generation sequencing approach after phage display selection with FSHR or its intracellular domains, we isolated and characterized several intra-VHHs, some of which also recognize LHCGR. Both receptors target gonadal cells and have key roles in orchestrating reproduction in Mammals. In my talk, I will present the functional impact of these intra-VHHs on FSHR and LHR signaling and trafficking and explain why these intra-VHHs may be useful to complement the structure/activity studies performed so far on gonadotropin receptors.

• Marie-Aude Hiebel, Institute of Organic and Analytical Chemistry (ICOA) / CNRS, University of Orléans - FR

  

  Marie-Aude Hiebel

  Institute of Organic and Analytical Chemistry (ICOA)

  Address:  Rue de Chartres, BP 6759, 45067 Orléans cedex 2 - France

   Email: marie-aude.hiebel@univ-orleans.fr

  Marie-Aude Hiebel earned her PhD in organic chemistry in 2008 from Université Claude Bernard Lyon 1. Her research focused on stereocontrolled syntheses of 2,6-disubstituted tetrahydropyrans and their application to total synthesis. She made a first postdoctoral stay at Upenn (Philadelphia, USA) and then she joined the University of Orléans (ICOA) in 2010 before being appointed lecturer in 2011. During five years, she developed environmentally sound methods to synthetize and modify nitrogen-containing heterocycles. In 2016, she joined CHeMBioLight group and since then she is involved in the development of organic fluorescent probes and also in various therapeutic programs. She is co-author of 44 publications and 2 patents and became an associate professor in July 2023.

  From Ligand Design to the biased Serodolin and a Tailor-Made BRET Assay: Integrated Pharmacological Evaluation of 5-HT7 Receptor Ligands

  The 5-HT7 receptor belongs to the G protein–coupled receptor (GPCR) superfamily and is positively coupled to adenylate cyclase, leading to increased intracellular cAMP levels. As the most recently identified serotonergic receptor, 5-HT7R is highly expressed in the central nervous system, particularly in the thalamus and hypothalamus, and is involved in key physiological functions such as memory, learning, and mood regulation. Owing to its therapeutic potential, the development of selective 5-HT7R ligands remains an important objective in medicinal chemistry.
  In this work, we report the design and synthesis of novel 5-HT7R ligands. A detailed structure–activity relationship (SAR) study was conducted, and the Serodolin ligand with original pharmacological profile was identified, acting as a high affinity 5-HT7R biased ligand able to engage different transducer–effector systems compared to classical agonists like 5-CT. More interestingly, this unprecedented biased effect on 5-HT7 receptors is not observed for other 5-HT7 ligands from the literature. Building on Serodolin, an innovative bioluminescence resonance energy transfer (BRET)-based affinity assay was developed using a fluorescent ligand as the energy acceptor. This tailor-made BRET assay provides a convenient and reliable method for determining ligand affinity, yielding results consistent with those obtained from conventional radioligand binding assays.

• Marcello Leopoldo, University of Bari Aldo Moro - IT

  

  Marcello Leopoldo

  University of Bari Aldo Moro 

  Address:  Dipartimento di Farmacia – Scienze del Farmaco, via Orabona 4, 70125 Bari - Italy

   Email: marcello.leopoldo@uniba.it

  Marcello Leopoldo is a full professor of Medicinal Chemistry at the University of Bari Aldo Moro (Italy). He has been studying the structure-activity relationships of small molecules targeting various G Protein-Coupled Receptors (GPCRs), including dopamine, serotonin, bombesin, and formyl peptide receptors, to identify drug-like selective agonists or antagonists as pharmacological tools, fluorescent probes, and positron emission tomography radioligands. He has authored more than 150 articles. One of the most relevant outcomes of his research is the brain-penetrant selective serotonin 5-HT7 receptor agonist LP-211, which indicated that 5-HT7 receptor activation may have therapeutic effects in neurodevelopmental diseases, such as Fragile X syndrome, Rett syndrome, and Angelman syndrome.

  Identification of the First-in-Class Photo-Activatable 5-HT7 Receptor Agonist

  The serotonin 5-HT7 receptor (5-HT7R) is a G protein-coupled receptor (GPCR) within the 5-HT receptor family, widely distributed across both peripheral tissues and the central nervous system (CNS). In the CNS, 5-HT₇R is expressed in limbic areas, the putamen, the raphe, the caudate nuclei, and cortical regions. This receptor plays a pivotal role in various physiological and pathophysiological processes, such as thermoregulation, circadian rhythm regulation, sleep, learning and memory, cognitive function, and stress response. Moreover, substantial evidence implicates 5-HT7R in mood disorders, including anxiety and depression. Investigating the specific roles of 5-HT7R in these complex processes poses significant challenges due to the intricate nature of CNS mechanisms. To this end, a photopharmacological approach might be of support. We will present the chemical design of a caged 5-HT7R agonist. Following the caging strategy, three photoprotective groups were attached to the basic nitrogen of two 5-HT7R ligands, resulting in reduced binding affinity. The new light-sensitive molecules release the agonist under suitable light conditions. The biological properties of the molecules released upon illumination have been studied in in vitro and ex vivo models, confirming that these tools can be used to study the role of 5-HT7R in a temporally controlled manner.

• Kara Margolis, New York University - USA

  

  Kara Margolis

  New York University

  Address:  433 First Avenue; NY, NY 10010 - USA

   Email: km5994@nyu.edu

  Kara Margolis is a Professor of Pediatrics and Cell biology at the NYU Grossman School of Medicine and a Professor of Molecular Pathobiology at the NYU College of Dentistry where she is also the Director for the NYU Pain Research Center. Dr. Margolis is a pediatric gastroenterologist and physician-scientist with clinical and scientific expertise in disorders that affect the gut and the brain, including abdominal pain-related disorders of gut brain interactions (DGBIs). In the laboratory, Dr. Margolis leads clinical, translational and basic science research programs whose themes center around the discovery of novel mediators that connect abdominal pain-linked disorders to mental health conditions like anxiety and depression.

  The role of serotonergic signaling in abdominal pain and mood dysfunction   

  Mood disorders and disorders of gut brain (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Though serotonergic drugs are often prescribed for both conditions, they are often unsuccessful and/or cause adverse effects.

  In this talk, Dr. Margolis will cover the patient presentations of these comorbid conditions, the physiology of gut serotonin in the context of mood and visceral pain and how we her laboratory has segued between mouse and human studies to develop a novel therapeutic concept for treating abdominal pain and mood disorders

• Mikołaj Matłoka, Celon Pharma SA - PL

  

  Mikołaj Matłoka

  Celon Pharma SA 

  Address:  R&D Centre, Marymoncka 15, 05-152 Kazuń Nowy - Poland

   Email: mikolaj.matloka@gmail.com

  Mikolaj Matloka is Head of Nonclinical Development – Neuropsychiatry group, at R&D Centre, Celon Pharma SA. He holds a degree in Molecular Biotechnology from the Technical University of Munich and earned his PhD in Biological Sciences from the Nencki Institute of Experimental Biology in Warsaw.
  He has over 15 years of experience in leading innovative drug development projects across various indications, spanning both early and late stages of development, including pharmacology, pharmacokinetics, toxicology, and regulatory support. He is a co-author of more than a dozen scientific publications and patents. Two of the molecules he helped develop have achieved positive results in Phase II clinical trials.

  CPL’298, a novel 5-HT7R agonist, with antinociceptive activity in animal models of neuropathic pain

  Neuropathic pain is a complex, chronic condition with limited treatment options for which there is high demand for new, efficient and safe therapies. CPL298 is a novel 5-HT7R agonist with robust drug-like properties undergoing advanced preclinical development and toxicological studies. CPL298 acts through activation of Gs protein leading to an increase in intracellular cAMP levels and phosphorylation of ERK1/2 and CREB which is PKA dependent. No increase in β-arrestin2 recruitment is observed upon its binding to the receptor. Activation of 5-HT7 receptor has been shown to have antinociceptive effects in animal models, making it a promising target for new therapies. CPL298 shows high efficacy in reducing both mechanical and thermal hypersensitivity, in a dose-dependent manner, in different pain models: chronic constriction injury (CCI) neuropathic pain model, streptozotocin (STZ)-induced diabetic neuropathy model and chemotherapy-induced peripheral neuropathy (CIPN) model in both acute and chronic settings, without any apparent behavioral side-effects. Pharmacokinetic properties of CPL298 strongly indicate that the antinociceptive action is achieved mostly peripheral, which serves as the starting point for further translational studies. 

• Séverine Morisset-Lopez, Center for Molecular Biophysics (CBM) - FR

  

  Séverine Morisset-Lopez

  Center for Molecular Biophysics (CBM) / CNRS

  Address: rue Charles Sadron, 45071 Orléans - France

   Email: severine.morisset-lopez@cnrs-orleans.fr

  Séverine Morisset-Lopez is a senior scientist at the Centre for Molecular Biophysics (Orléans, France) with recognized expertise in neuropharmacology and GPCR biology. She has contributed significantly to the molecular study of histamine and serotonin receptors, providing key insights into their regulation and therapeutic targeting in neurodegenerative and psychiatric disorders. Her group develops innovative BRET-based assays to study GPCR signaling and screen drug candidates, which are further evaluated in cellular and murine preclinical models. Her current research focuses on the pharmacology of the serotonin 5-HT7 receptor, its biased signaling, and its role in pain and neuroinflammatory diseases such as multiple sclerosis and chronic pain. 

  Biased 5-HT7 receptor ligands as promising analgesics targeting spinal neuroinflammation

  G protein-coupled receptors (GPCRs) signal through both G proteins and β-arrestin–dependent pathways. Ligands that selectively activate these pathways, known as biased ligands, offer new opportunities to modulate GPCR signaling with improved therapeutic efficacy and fewer side effects.
  The serotonin 5-HT7 receptor (5-HT7R) has emerged as a promising therapeutic target for neuropsychiatric disorders, circadian rhythm disturbances, and pathological pain. We previously identified Serodolin, a small molecule that binds to 5-HT7R with nanomolar affinity and exhibits biased activity. Serodolin acts as an antagonist/inverse agonist on Gs-mediated signaling while promoting ERK activation through a β-arrestin–dependent mechanism involving c-SRC. In vivo, Serodolin significantly reduced hyperalgesia induced by inflammatory, thermal, and mechanical stimuli. These effects were absent in 5-HT7R knockout mice and blocked by the selective antagonist SB269-970, confirming receptor specificity.
  We subsequently identified a second biased ligand, MOA51, and compared the pharmacological profiles of both compounds. In inflammatory pain models (acetic acid writhing, formalin, CFA), both ligands significantly reduced nociceptive responses. In neuropathic pain models (SNI and Cuff), they reversed mechanical allodynia and reduced neuroinflammatory processes.
  These findings highlight the potential of 5-HT7R-biased ligands as innovative analgesic candidates for inflammatory and neuropathic pain.

• Evgeni Ponimaskin, Hannover Medical School - DE

  

  Evgeni Ponimaskin

  Dept. of Cellular Neurophysiology, Institute of Neurophysiology, Hannover Medical School 

  Address:  Carl-Neuberg-Str. 1, 30627 Hannover, Germany

   Email: Ponimaskin.Evgeni@mh-hannover.de

  Prof. Dr. Evgeni Ponimaskin is Professor of Cellular Neurophysiology at Hannover Medical School, Germany. He studied biochemistry at the University of Oldenburg and received his PhD from the Free University Berlin. After postdoctoral training in Berlin and Göttingen, he became group leader at the DFG Research Center “Molecular Physiology of the Brain” in Göttingen and obtained his habilitation in physiology. Since 2008 he heads the Department of Cellular Neurophysiology in Hannover. His research focuses on molecular mechanisms of neurodegeneration, particularly serotonin receptor signalling, tau pathology, and therapeutic strategies for tauopathies using cellular and animal models.

  Serotonin 5-HT7 Receptor as a Therapeutic Target in Tauopathies: From Mechanism to Intervention  

  Aggregation of the microtubule-associated protein Tau drives tauopathies, including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Although the serotonergic system has re-emerged as a therapeutic target in neurodegeneration, the contribution of specific serotonin receptors to pathological Tau aggregation remained unclear.
  We identified a causal link between the constitutive activity of the serotonin GPCR 5-HT7 (5-HT7R) and pathological Tau hyperphosphorylation as well as neurofibrillary tangle formation in primary neurons and cortical neurons in vivo. Mechanistically, 5-HT7R physically interacts with the Tau kinase CDK5, inducing its G protein-independent activation. We defined the structural determinants of the 5-HT7R–CDK5 interaction and mapped their binding interface.
  Structural and functional screening identified clinically approved drugs with strong inverse agonism at 5-HT7R, with amisulpride emerging as a lead compound. Using biochemical, pharmacological, imaging, and behavioral analyses in primary mouse neurons, human iPSC-derived neurons carrying an FTD-associated Tau mutation, and two tauopathy mouse models, we demonstrated that amisulpride reduces Tau hyperphosphorylation, tangle formation, apoptosis, and memory deficits. We have also initiated treatment of three FTD patients under individual therapeutic use. Moreover, we optimized amisulpride structure to enhance 5-HT7R selectivity and reduce side effects.  
  These findings establish inverse agonism at 5-HT7R as a novel therapeutic strategy for tauopathies.

• Raphaël Serreau, Center for Molecular Biophysics (CBM) - FR

  

  Raphaël Serreau

  Center for Molecular Biophysics (CBM) / CNRS

  Address:  3E avenue de la recherche scientifique  45071 Orléans - France

   Email: raphael.serreau@cnrs-orleans.fr

  After completing my residency in public health at the Paris Hospitals, I worked for 20 years as a university hospital assistant and hospital practitioner in clinical pharmacology at the AP-HP in Paris. I worked on the transfer of drugs from mother to child during pregnancy and breastfeeding. In 2025, I became a full Professor at the Orléans University Hospital in the addiction department at the EPSM du Loiret. Scientist at the CNRS in the NEURRIT team, where my work focuses on the use of psychedelics to promote alcohol abstinence, while supervising three doctoral students in the field of mental health. I’ve published more than 50 papers in the area of toxicology, drugs, pregnancy and breastfeeding. I’m interested in developing new molecules to prevent alcohol use disorders (AUD).

  Psychedelics in alcohol use disorders: a strong pharmacologic innovation

  Alcohol use disorders a psychiatric condition characterized by excessive alcohol consumption. Patients are often caught in a cycle of abstinence and relapse. They also frequently experience heavy drinking days, defined as the consumption of at least five standard unit (SU) per day for men and four SU per day for women. Conventional antidepressants generally show poor efficacy in treating AUD. Drugs such as serotonin reuptake inhibitors (SSRI), including fluoxetine are used in treatment but often fail to prevent relapse. At the same time, psilocybin, a natural psychedelic is increasingly being investigated for the treatment of various substance use disorders. Psilocybin is a potent agonist of serotonin receptors, particularly 5-HT2A receptors and is currently being explored as a potential therapeutic option for AUD with ongoing and planned clinical studies in 2026. The synthesis of a few milligrams of psilocin was possible in our lab with the collaboration of Pr Sabine Berteina-Raboin (ICOA). It has enabled initial in vitro pharmacological studies to be carried out to assess the stability and receptor affinity of the molecule in cellular models. These studies now need to be strengthened and expanded, both by optimizing synthetic pathways to obtain larger quantities of psilocin, by conducting translational research approaches combining fundamental, preclinical, and clinical studies in individuals with alcohol use disorder. According to recent clinical trials, psilocybin seems to reduce craving, although its effect on overall alcohol consumption remains less clearly established. There is no doubt that future trials would benefit from larger sample sizes and the use of standardized outcome measures.

• Stephanie Watts, Michigan State University - USA

  

  Stephanie Watts

  Michigan State University

  Address: Dept of Pharmacology & Toxicology, East Lansing, MI, 48824-1317 USA

   Email: wattss@msu.edu

  Stephanie Watts is dedicated to understanding vascular dysfunction in hypertension and obesity.  We focus on serotonin, chemerin and perivascular adipose tissue (PVAT).  She has received grants from the NIH, American Heart Association (Established Investigator) and pharmaceutical industry. She serves as the Director of an NHLBI funded Program Project grant invested in discovering new functions of PVAT, and chairs a Cardiometabolic effort between MSU and HFHS.  She has been on multiple NIH study sections, associate editor (Pharm Res, Pharm Rev, AJH) and PhRMA Foundation and Keystone Scientific Advisory Boards.  She is a fellow of Council on Hypertension, APS and ASPET and is an MSU Beal Professor.  She is committed to mentoring, having the privilege of ~120 trainees pass through her laboratory.  ALL students learn about 5-HT! Pharmacology is the river that runs through Dr. Watts’ career.  Thewattslab.com, pvatppgmsu.com. 

   The 5-HT7 receptor as a druggable target for treatment of (resistant) hypertension

  Hypertension is the #1 modifiable factor for lowering risk of cardiovascular disease.  The management of hypertension faces the challenge of: regression of blood pressure control; resistance (uncontrolled with 3 meds); and refractoriness (uncontrolled with 5 meds).  This sobering problem is the impetus for new discoveries which step outside of traditional therapies.  We have spent decades understanding how serotonin (5-hydroxytryptamine, 5-HT) reduces blood pressure.  Venous and arteriole relaxation are mediated by the 5-HT7 receptor, validated by use of a 5-HT7 receptor knockout rat we created.  The activated 5-HT7 receptor suppresses 5-HT2A receptor mediated contraction. Data support that it is the Gs pathway stimulated by the receptor necessary for these actions.  The b-arrestin 5-HT7 receptor agonist Serodolin did not cause vascular relaxation or hypotension via the b -arrestin pathway but acted as a 5-HT2A receptor antagonist and as a functional 5-HT7 receptor antagonist in vitro.  Importantly, 5-HT reduces blood pressure in a rat model that is resistant to diuretics.  Thus, activation of the Gs pathway of the 5-HT7 receptor may prove beneficial in two ways:  activating a relaxant receptor and promoting restraint of the contractile 5-HT2A receptor.  Collectively, these studies point to the significant utility of creating new molecules that can activate the 5-HT7 receptor in a Gs biased way for treatment of hypertensions that are not controlled. 

• Paweł Zajdel, Jagiellonian University Medical College - PL

  

  Paweł Zajdel

  Jagiellonian University Medical College

  Address:  9 Medyczna Street - Poland

   Email: pawel.zajdel@uj.edu.pl

  Paweł Zajdel is a medicinal chemist whose research focuses on designing ligands for GPCR, with particular emphasis on serotonin and dopamine modulators relevant to psychiatric, neurodegenerative and neurological disorders. His work also involves developing molecular probes that target distinct conformational states and signaling pathways of GPCRs. Recent efforts center on dual-acting ligands that leverage synergistic mechanisms to more effectively address complex CNS pathologies He obtained his PhD in 2006 through a joint program between the Jagiellonian University Medical College and the University of Montpellier. He has co-authored over 100 publications and currently heads the Chair of Bioorganic Chemistry at Jagiellonian University Medical College in Kraków.

  Fine-tuning 5-HT7 receptor inverse agonism: identification of PZ-2172 with favorable ADME/T profile and MMP-9 mediated antidepressant properties

  Robust evidence support the concept that 5-HT7 receptor inverse agonists may offer a promising therapeutic strategy for CNS disorders. This receptor, a Gs-coupled GPCR characterized by high level of constitutive activity, has been implicated in depressive-like behavior. Building on these findings, we continued our efforts to development novel 5-HT7 receptor ligands in a group of arylsulfonamide derivatives of (aryloxy)alkyl alicyclic amines. Through this work, we identified PZ-2172 as a lead with favorable pharmacological properties.

  PZ‑2172 is a potent and selective 5-HT7 inverse agonist at Gs signaling, showing favorable in vitro ADME/T characteristics and good in vivo brain penetration. In rodents, it demonstrates antidepressant-like effects at 0.5 mg/kg (ip) and pro-cognitive activity at 1 mg/kg (ip). PZ-2172 also reverses anhedonia in the Sucrose Preference Test and reduces immobility in the Tail Suspension Test in the chronic restraint stress (CRS) model. It also reduces 5-HT7-mediated MMP-9 activity in relevant brain regions after acute administration and under CRS conditions, with potency comparable to the reference inverse agonist SB-269970. These results support further studies to validate the therapeutic potential of targeting the 5-HT7/MMP-9 signaling pathway in affective disorders.

  The studies were partially funded by the National Science Centre, Poland, grant no 2019/33/B/NZ7/02822.

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