Medicinal Chemistry for the Modulation of Synaptic Transmission

The group is focused on small molecules that target receptors and transporters of synaptic transmission and their mechanisms. Using synthetic organic chemistry and molecular modeling, we develop pharmacological and therapeutic tools and investigate receptor activation and neurotransmitter transport. The team is involved in various projects from the initial design (molecules, 3D models…) all along to the in vivo studies. The interdisciplinary projects are made possible through numerous collaborations in the fields of pharmacology, molecular biology, cellular biology and behavior. Thus, molecules that are developed in the group allow investigations of animal models of Parkinson’s disease motor symptoms, psychiatric diseases, epilepsy, cognition, pain and addiction as well as imaging and activation or transport mechanism elucidation. Our research spans over two major fields that are actually linked in the synaptic event: Class C G Protein Coupled Receptors (GPCRs) and neuronal transporters. More recently, we initiated with the Metabolism group, the Tryptophan metabolism project based on our experience with cinnabarinic acid and its effect on metabotropic glutamate receptor 4.

Key words:
selective orthosteric ligands, transporter inhibitors, glutamate, probe synthesis, structure-activity relationship, small molecule-protein interaction, structure function studies, docking, virtual high throughput screening, hit optimization.



  • Dr J.-P. PIN Institute for Functional Genomics, Molecular Pharmacology Department, Montpellier, France
  • Dr H.-O. BERTRAND and GOUPIL-LAMY Biovia/Dassault Systems, Velizy , France
  • Dr J. WIERONSKA and A. PILC, Institute of Pharmacology, Krakow, Poland
  • Dr F. BERTASO, Institute for Functional Genomics, Montpellier, France
  • Dr F. FAZIO and N. NICOLETTI, Physiology and Pharmacology, Neuromed, Pozzilli, Italy
  • Dr L. MONY and Dr P. PAOLETTI, Laboratoire de Neurobiologie, Ecole Normale Supérieure, Paris, France
  • Dr B. GASNIER CNRS University Paris Descartes, France
  • Dr N. MARIE and Dr F. NOBLE CNRS University Paris Descartes, France
  • Dr J.-P. MOTHET, Univ Paris Saclay, France
  • Dr R. NGOMBA University of Lincoln, UK
  • Pr P. FLOR, University of Regensburg, Germany
  • Dr M. BLANCHARD-DESCE, University of Bordeaux, France
  • Dr A. LLEBARIA Institute of Advanced Chemistry of Catalonia (IQAC), Barcelona, Spain
  • Pr U. ISACOFF University of California Berkeley (USA)

 Science Outreach

 Épilepsie : une nouvelle piste thérapeutique identifiée

Molecular discovery at Université de Paris could improve treatment for Parkinson’s patients

Portraits of Sustainability Pioneers: Dassault Systèmes presents Francine Acher of Univ. de Paris

Recent Publications


(1) B. Girard, P. Tuduri, M. P. Moreno, S. Sakkaki, C. Barboux, T.Bouschet, A. Varrault, J. Vitre, I. McCort, J. Dairou, F. Acher, L. Fagni, N. Marchi, J. Perroy, F. Bertaso The mGlu7 receptor provides new protective effects against epileptogenesis and epileptic seizures. Neurobiology of disease 2019, 129, 13-28. doi: 10.1016/j.nbd.2019.04.016.

(2) Maya Kansara, Kristian Thomson, Puiyi Pang, Aurelie Dutour, Lisa Mirabello, Francine Acher, Jean-Philippe Pin, Michele W.L. Teng, Juming Yan, Mark J. Smyth, David M. Thomas. Infiltrating Myeloid Cells Drive Osteosarcoma Progression via GRM4 Regulation of IL23. Cancer Discovery 2019, 9(11):1511-1519; doi: 10.1158/2159-8290.CD-19-0154.

(3) Orrico-Sanchez A., Chausset-Boissarie L., Alves de Sousa R., Coutens B., Rezai Amin S., Vialou V., Louis F., Hessani A., Dansette P.M., Zornoza T., Gruszczynski C., Giros B., Guiard B.P., Acher F., Pietrancosta N., Gautron S. Antidepressant efficacy of a selective organic cation transporter blocker in a mouse model of depression. Mol Psychiatry 2019 doi: 10.1038/s41380-019-0548-4. [Epub ahead of print]

(4) Habrian C., Levitz J., Vyklicky V., Fu Z., Hoagland A., McCort-Tranchepain I., Acher F. and Isacoff E. Y. Novel conformational pathway provides unique sensitivity and dynamics to a synaptic mGluR. Nature Commun 2019, accepted


(1) Zussy, C.; Gómez-Santacana, X.; Rovira, X.; De Bundel, D.; Ferrazzo, S.; Bosch, D.; Asede, D.; Malhaire, F.; Acher, F.; Giraldo, J.; Valjent, E.; Ehrlich, I.; Ferraguti, F.; Pin, J.-P.; Llebaria, A.; Goudet, C. Dynamic modulation of inflammatory pain-related affective and sensory symptoms by optical control of amygdala metabotropic glutamate receptor 4. Mol Psychiatry 2018, 23, 509-520. doi: 10.1038/mp.2016.223.

(2) Hajasova, Z., Canestrelli, C., Acher, F., Noble F., Marie N., Role of mGlu7 receptor in morphine rewarding effects is uncovered by a novel orthosteric agonist. Neuropharmacology 2018, 131, 424-430.

(3) Lebourgeois S., Vilpoux C., Acher F., Marie N., Noble F., Naassila M. Pharmacological activation of mGluR4 and mGluR7, by LSP2-9166, reduces ethanol consumption and relapse in rat. Neuropharmacology 2018, 133, 163-170. doi: 10.1016/j.neuropharm.2018.01.031

(4) Selvam, C., Lemasson, I. A., Brabet, I., Oueslati, N., Karaman, B., Cabaye, A., Tora, A. S., Commare, B., Courtiol, T., Cesarini, S., McCort-Tranchepain, I., Rigault, D., Mony, L., Bessiron, T., McLean, H., Leroux, F. R., Colobert, F., Daniel, H. Goupil-Lamy, A., Bertrand, H.-O., Goudet, C., Pin, J.-P. and Acher, F. C. Increased potency and selectivity for group-III metabotropic glutamate receptor agonists binding at dual sites. J Med Chem 2018, 61, 1969-1989. doi: 10.1021/acs.jmedchem.7b01438

(5) Goudet, C.; Rovira, X.; Rondard, P.; Pin, J.-P.; Llebaria, A.; Acher, F. Modulation of Metabotropic Glutamate Receptors by Orthosteric, Allosteric, and Light-Operated Ligands. Springer International Publishing AG: 2018; p 32.

(6) Cieślik, P., Woźniak, M., Rook, J.M., Tantawy, M.N., Conn, P.J., Acher, F., Tokarski, K., Kusek, M., Pilc, A., Wierońska, J.M. Mutual activation of glutamatergic mGlu4 and muscarinic M4 receptors reverses schizophrenia related changes in rodents. Psychopharmacology 2018, 235(10), 2897-2913 doi: 10.1007/s00213-018-4980-y.

(7) Belhocine A, Veglianese P, Hounsou C, Dupuis E, Acher F, Durroux T, Goudet C, Pin JP. Profiling of orthosteric and allosteric group-III metabotropic glutamate receptor ligands on various G protein-coupled receptors with Tag-lite® assays. Neuropharmacology 2018, 140, 233-245; doi: 10.1016/j.neuropharm.2018.07.032.

(8) Tora AS, Rovira X, Cao AM, Cabayé A, Olofsson L, Malhaire F, Scholler P, Baik H, Van Eeckhaut A, Smolders I, Rondard P, Margeat E, Acher F, Pin JP, Goudet C. Chloride ions stabilize the glutamate-induced active state of the metabotropic glutamate receptor 3. Neuropharmacology 2018, 140, 275-286; doi: 10.1016/j.neuropharm.2018.08.011.


(1) Smith N, Pietrancosta N, Davidson S, Dutrieux J, Chauveau L, Cutolo P, Dy M, Scott-Algara D, Manoury B, Zirafi O, McCort-Tranchepain I, Durroux T, Bachelerie F, Schwartz O, Münch J, Wack A, Nisole S, Herbeuval JP. Natural amines inhibit activation of human plasmacytoid dendritic cells through CXCR4 engagement. Nat Commun. 2017 Feb 9;8:14253. doi: 10.1038/ncomms14253.

(2) Woźniak M, Gołembiowska K, Noworyta-Sokołowska K, Acher F, Cieślik P, Kusek M, Tokarski K, Pilc A, Wierońska JM. Neurochemical and behavioral studies on the 5-HT1A-dependent antipsychotic action of the mGlu4 receptor agonist LSP4-2022. Neuropharmacology 2017, 115, 149-165.


(1) Tassin, V.; Girard, B.; Chotte ,A.; Fontanaud, P.; Rigault, D.; Kalinichev, M.; Perroy, J.; Acher, F.; Fagni, L. and Bertaso, F. Phasic and Tonic mGlu7 Receptor Activity Modulates the Thalamocortical Network. Frontiers in neural circuits 2016, 31, article number 31.

(2) Wozniak, M.; Wieronska, J. M.; Acher, F.; Marciniak, M.; Lason-Tyburkiewicz, M.; Gruca, P.; Papp, M. and Pilc, A. Involvement of GABAB signaling in the Antipsychotic-like Action of the Novel Orthosteric Agonist of mGlu4 Receptor, LSP4-2022. Cur Neuropharmacology 2016, 14(5), 413-426.

For older See PubMed