Basimglurant for treatment of major depressive disorder: a novel negative allosteric modulator of metabotropic glutamate receptor 5

EVIDENCE FOR THE EXISTENCE OF MONOAMINE-CONTAINING NEURONS IN THE CENTRAL NERVOUS SYSTEM. I. DEMONSTRATION OF MONOAMINES IN THE CELL BODIES OF BRAIN STEM NEURONS.

Dahlstroem, A., & Fuxé, K. (1964) · PubMed · Cited by 5,143 · see citing works

A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.

Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., Charney, D. S., & Manji, H. K. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.8.856 · Cited by 3,766 · see citing works

NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses

Autry, A. E., Adachi, M., Nosyreva, E., Na, E. S., Los, M. F., Cheng, P.-F., Kavalali, E. T., & Monteggia, L. M. (2011) · Nature · doi:10.1038/nature10130 · Cited by 1,926 · see citing works

Synaptic Dysfunction in Depression: Potential Therapeutic Targets

Duman, R. S., & Aghajanian, G. K. (2012) · Science · doi:10.1126/science.1222939 · Cited by 1,651 · cited 3× · see citing works

Towards a glutamate hypothesis of depression

Sanacora, G., Treccani, G., & Popoli, M. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.07.036 · Cited by 1,036 · see citing works

A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression

Diazgranados, N., Ibrahim, L., Brutsche, N. E., Newberg, A., Kronstein, P., Khalife, S., Kammerer, W. A., Quezado, Z., Luckenbaugh, D. A., Salvadore, G., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.90 · Cited by 963 · see citing works

Functional antagonists at the NMDA receptor complex exhibit antidepressant actions

Trullas, R., & Skolnick, P. (1990) · European Journal of Pharmacology · doi:10.1016/0014-2999(90)90204-j · Cited by 785 · see citing works

Monoamine neurocircuitry in depression and strategies for new treatments

Hamon, M., & Blier, P. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.04.009 · Cited by 643 · see citing works

Mice Lacking Metabotropic Glutamate Receptor 5 Show Impaired Learning and Reduced CA1 Long-Term Potentiation (LTP) But Normal CA3 LTP

Lu, Y.-M., Jia, Z., Janus, C., Henderson, J. T., Gerlai, R., Wojtowicz, J. M., & Roder, J. C. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-13-05196.1997 · Cited by 634 · see citing works

An Innovative Design to Establish Proof of Concept of the Antidepressant Effects of the NR2B Subunit Selective N-Methyl-D-Aspartate Antagonist, CP-101,606, in Patients With Treatment-Refractory Major Depressive Disorder

Preskorn, S., Baker, B., Kolluri, S., Menniti, F. S., Krams, M., & Landen, J. W. (2008) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31818a6cea · Cited by 522 · see citing works

A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei

Pollak Dorocic, I., Fürth, D., Xuan, Y., Johansson, Y., Pozzi, L., Silberberg, G., Carlén, M., & Meletis, K. (2014) · Neuron · doi:10.1016/j.neuron.2014.07.002 · Cited by 451 · see citing works

Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain

Dore, A. S., Okrasa, K., Patel, J. C., Serrano‐Vega, M. J., Bennett, K. A., Cooke, R. M., Errey, J. C., Jazayeri, A., Khan, S. A., Tehan, B. G., et al. (2014) · Nature · doi:10.1038/nature13396 · Cited by 410 · see citing works

Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond

Krystal, J. H., Sanacora, G., & Duman, R. S. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.03.026 · Cited by 406 · see citing works

Glutamate-based antidepressants: 20 years on

Skolnick, P., Popik, P., & Trullás, R. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.09.002 · Cited by 382 · see citing works

mTOR complexes in neurodevelopmental and neuropsychiatric disorders

Costa-Mattioli, M., & Monteggia, L. M. (2013) · Nature Neuroscience · doi:10.1038/nn.3546 · Cited by 367 · see citing works

Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: Implications for striatal neuronal function

Ferré, S., Karcz‐Kubicha, M., Hope, B. T., Popoli, P., Burgueño, J., Gutiérrez, M. A., Casadó, V., Fuxé, K., Goldberg, S. R., Lluı́s, C., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172393799 · Cited by 365 · see citing works

GluN2B-containing NMDA receptors regulate depression-like behavior and are critical for the rapid antidepressant actions of ketamine

Miller, O. H., Yang, L., Wang, C.-C., Hargroder, E. A., Zhang, Y., Delpire, E., & Hall, B. J. (2014) · eLife · doi:10.7554/elife.03581 · Cited by 358 · see citing works

Efficacy and effectiveness of antidepressants: current status of research

Pigott, H. E., Leventhal, A. M., Alter, G. S., & Boren, J. J. (2010) · Psychotherapy and Psychosomatics · doi:10.1159/000318293 · Cited by 347 · cited 1× · see citing works

Molecular Mechanisms and Therapeutical Implications of Intramembrane Receptor/Receptor Interactions among Heptahelical Receptors with Examples from the Striatopallidal GABA Neurons

Agnati, L. F., Ferré, S., Lluı́s, C., Franco, R., & Fuxé, K. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.3.2 · Cited by 322 · see citing works

Role of dopamine receptor mechanisms in the amygdaloid modulation of fear and anxiety: Structural and functional analysis

de la Mora, M. P., Gallegos-Cari, A., Arizmendi-García, Y., Marcellino, D., & Fuxe, K. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.10.010 · Cited by 296 · see citing works

Acute suppression of spontaneous neurotransmission drives synaptic potentiation

Nosyreva, E., Szabla, K., Autry, A. E., Ryazanov, A. G., Monteggia, L. M., & Kavalali, E. T. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4998-12.2013 · Cited by 283 · cited 1× · see citing works

Reduced Metabotropic Glutamate Receptor 5 Density in Major Depression Determined by [¹¹C]ABP688 PET and Postmortem Study

Deschwanden, A., Karolewicz, B., Feyissa, A. M., Treyer, V., Ametamey, S. M., Johayem, A., Burger, C., Auberson, Y. P., Sovago, J., Stockmeier, C. A., et al. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.09111607 · Cited by 278 · see citing works

An excitatory synapse hypothesis of depression

Thompson, S. M., Kallarackal, A. J., Kvarta, M. D., Van Dyke, A. M., LeGates, T. A., & Cai, X. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.03.003 · Cited by 265 · see citing works

Metabotropic glutamate type 5, dopamine D2 and adenosine A2a receptors form higher‐order oligomers in living cells

Cabello, N., Gandía, J., Bertarelli, D. C. G., Watanabe, M., Lluı́s, C., Franco, R., Ferré, S., Luján, R., & Ciruela, F. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06078.x · Cited by 253 · see citing works

Functional Interaction Between NMDA and mGlu5 Receptors: Effects on Working Memory, Instrumental Learning, Motor Behaviors, and Dopamine Release

Homayoun, H., Stefani, M. R., Adams, B. W., Tamagan, G. D., & Moghaddam, B. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300417 · Cited by 252 · see citing works

From the Golgi–Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: Wiring and volume transmission

Fuxé, K., Dahlström, A. B., Höistad, M., Marcellino, D. J., Jansson, A., Rivera, A., Dı́az-Cabiale, Z., Jacobsen, K. R., Tinner, B., Hagman, B., et al. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.02.009 · Cited by 247 · see citing works

Receptor heteromerization in adenosine A 2A receptor signaling

Fuxé, K., Agnati, L. F., Jacobsen, K. R., Hillion, J., Canals, M., Torvinen, M., Tinner, B., Staines, W. A., Rosin, D. L., Terasmaa, A., et al. (2003) · Neurology · doi:10.1212/01.wnl.0000095206.44418.5c · Cited by 246 · see citing works

Development of allosteric modulators of GPCRs for treatment of CNS disorders

Nickols, H. H., & Conn, P. J. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.09.013 · Cited by 227 · see citing works

Phenylethanolamines inhibit NMDA receptors by enhancing proton inhibition

Mott, D. D., Doherty, J., Zhang, S., Washburn, M. S., Fendley, M. J., Lyuboslavsky, P. N., Traynelis, S. F., & Dingledine, R. J. (1998) · Nature Neuroscience · doi:10.1038/3661 · Cited by 224 · see citing works

Enhancement of NMDA responses by group I metabotropic glutamate receptor activation in striatal neurones

Pisani, A., Calabresi, P., Centonze, D., & Bernardi, G. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0700999 · Cited by 211 · see citing works

The effect of imipramine of central 5-hydroxytryptamine neurons

Carlsson, A., Fuxé, K., & Ungerstedt, U. (1968) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1968.tb09706.x · Cited by 196 · see citing works

Important messages in the ‘post’: recent discoveries in 5-HT neurone feedback control

Sharp, T., Boothman, L. J., Raley, J., & Quérée, P. (2007) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2007.10.009 · Cited by 190 · see citing works

Reevaluation of the indoleamine hypothesis of depression. Evidence for a reduction of functional activity of central 5-HT systems by antidepressant drugs

Ögren, S. O., Fuxé, K., Agnati, L. F., Gustafssons, J. �., JONSSON, G., & Holm, A. C. (1979) · Journal of Neural Transmission · doi:10.1007/bf01250331 · Cited by 181 · see citing works

Mood disorders: Regulation by metabotropic glutamate receptors

Pilc, A., Chaki, S., Nowak, G., & Witkin, J. M. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.09.021 · Cited by 163 · see citing works

Metabotropic Glutamate 5 Receptor Antagonism Is Associated with Antidepressant-Like Effects in Mice

Li, X., Need, A. B., Baez, M., & Witkin, J. M. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.103143 · Cited by 163 · see citing works

Heterodimerization of Calcium Sensing Receptors with Metabotropic Glutamate Receptors in Neurons

Gama, L., Wilt, S. G., & Breitwieser, G. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105662200 · Cited by 157 · see citing works

Antidepressant actions of ketamine: from molecular mechanisms to clinical practice

Monteggia, L. M., & Zarate, C. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.12.004 · Cited by 149 · see citing works

Differential Expression of Group I Metabotropic Glutamate Receptors in Functionally Distinct Hippocampal Interneurons

van Hooft, J. A., Giuffrida, R., Blatow, M., & Monyer, H. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-10-03544.2000 · Cited by 141 · see citing works

The Selective mGlu5 Receptor Agonist CHPG Inhibits Quinpirole-Induced Turning in 6-Hydroxydopamine-Lesioned Rats and Modulates the Binding Characteristics of Dopamine D2 Receptors in the Rat Striatum Interactions with Adenosine A2a Receptors

Popoli, P. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00256-1 · Cited by 136 · see citing works

The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components

Borroto-Escuela, D., Brito, I., Romero-Fernandez, W., Di Palma, M., Oflijan, J., Skieterska, K., Duchou, J., Van Craenenbroeck, K., Suárez-Boomgaard, D., Rivera, A., et al. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15058570 · Cited by 134 · see citing works

Fibroblast Growth Factor Receptor 1– 5-Hydroxytryptamine 1A Heteroreceptor Complexes and Their Enhancement of Hippocampal Plasticity

Borroto‐Escuela, D. O., Romero‐Fernandez, W., Mudò, G., Pérez‐Alea, M., Ciruela, F., Tarakanov, A. O., Narváez, M., Liberto, V. D., Agnati, L. F., Belluardo, N., et al. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.09.012 · Cited by 126 · see citing works

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

Borroto‐Escuela, D. O., Agnati, L. F., Bechter, K., Jansson, A., Tarakanov, A. O., & Fuxé, K. (2015) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2014.0183 · Cited by 121 · see citing works

Distribution of Extrasynaptic NMDA Receptors on Neurons

Petralia, R. S. (2012) · The Scientific World JOURNAL · doi:10.1100/2012/267120 · Cited by 121 · see citing works

mGlu2/3 and mGlu5 receptors: Potential targets for novel antidepressants

Chaki, S., Ago, Y., Pałucha-Poniewiera, A., Matrisciano, F., & Pilc, A. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.05.022 · Cited by 114 · see citing works

Pharmacology of Basimglurant (RO4917523, RG7090), a Unique Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator in Clinical Development for Depression

Lindemann, L., Porter, R. H., Scharf, S. H., Kuennecke, B., Bruns, A., von Kienlin, M., Harrison, A. C., Paehler, A., Funk, C., Gloge, A., et al. (2015) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.222463 · Cited by 107 · see citing works

Metabotropic glutamate receptor 5 as drug target for Fragile X syndrome

Scharf, S. H., Jaeschke, G., Wettstein, J. G., & Lindemann, L. (2015) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2014.11.004 · Cited by 106 · see citing works

Allosteric Potentiators of Metabotropic Glutamate Receptor Subtype 5 Have Differential Effects on Different Signaling Pathways in Cortical Astrocytes

Zhang, Y., Rodriguez, A. L., & Conn, P. J. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.090308 · Cited by 102 · see citing works

Moonlighting Proteins and Protein–Protein Interactions as Neurotherapeutic Targets in the G Protein-Coupled Receptor Field

Fuxé, K., Borroto‐Escuela, D. O., Romero‐Fernandez, W., Palkovits, M., Tarakanov, A. O., Ciruela, F., & Agnati, L. F. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.242 · Cited by 101 · see citing works

Positive Allosteric Modulation of Metabotropic Glutamate 5 (mGlu5) Receptors Reverses N-Methyl-D-Aspartate Antagonist-Induced Alteration of Neuronal Firing in Prefrontal Cortex

Lecourtier, L., Homayoun, H., Tamagnan, G. D., & Moghaddam, B. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.12.003 · Cited by 101 · see citing works

Galanin receptor-1 modulates 5-hydroxtryptamine-1A signaling via heterodimerization

Borroto‐Escuela, D. O., Narváez, M., Marcellino, D. J., Parrado, C., Narváez, J. Á., Tarakanov, A. O., Agnati, L. F., Dı́az-Cabiale, Z., & Fuxé, K. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.02.078 · Cited by 98 · see citing works

Facilitation of gaba release by neurotensin is associated with a reduction of dopamine release in rat nucleus accumbens

Tanganelli, S., O'Connor, W. T., Ferraro, L., Bianchi, C., Beani, L., Ungerstedt, U., & Fuxé, K. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90493-6 · Cited by 97 · see citing works

Localization of 5-hydroxytryptamine uptake in rat brain after intraventricular injection

Fuxé, K., & Ungerstedt, U. (1967) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1967.tb08097.x · Cited by 94 · see citing works

On the mechanism of action of the antidepressant drugs amitriptyline and nortriptyline. Evidence for 5-hydroxytryptamine receptor blocking activity

Fuxé, K., Ögren, S. O., Agnati, L. F., Gustafsson, J. Å., & JONSSON, G. (1977) · Neuroscience Letters · doi:10.1016/0304-3940(77)90095-7 · Cited by 91 · see citing works

Metabotropic glutamate receptors as drug targets: what's new?

Nicoletti, F., Bruno, V., Ngomba, R. T., Gradini, R., & Battaglia, G. (2014) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2014.12.002 · Cited by 90 · see citing works

Translating A2Aantagonist KW6002 from animal models to parkinsonian patients

Chase, T. N., Bibbiani, F., Bara‐Jimenez, W., Dimitrova, T. D., & Oh-Lee, J. D.-H. (2003) · Neurology · doi:10.1212/01.wnl.0000095223.08711.48 · Cited by 86 · see citing works

Dopamine heteroreceptor complexes as therapeutic targets in Parkinson’s disease

Fuxé, K., Guidolin, D., Agnati, L. F., & Borroto‐Escuela, D. O. (2014) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.981529 · Cited by 80 · see citing works

A Novel Metabotropic Glutamate Receptor 5 Positive Allosteric Modulator Acts at a Unique Site and Confers Stimulus Bias to mGlu5 Signaling

Noetzel, M. J., Gregory, K. J., Vinson, P. N., Manka, J. T., Stauffer, S. R., Lindsley, C. W., Niswender, C. M., Xiang, Z., & Conn, P. J. (2013) · Molecular Pharmacology · doi:10.1124/mol.112.082891 · Cited by 77 · see citing works

Neurotransmitter Targeting in the Treatment of Depression

Blier, P. (2013) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.12084su1c.04 · Cited by 76 · see citing works

Mice lacking NMDA receptors in parvalbumin neurons display normal depression-related behavior and response to antidepressant action of NMDAR antagonists

Pozzi, L., Dorocic, I. P., Wang, X., Carlén, M., & Meletis, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0083879 · Cited by 74 · see citing works

Extrasynaptic Neurotransmission in the Modulation of Brain Function. Focus on the Striatal Neuronal–Glial Networks

Fuxé, K., Borroto‐Escuela, D. O., Romero‐Fernandez, W., Dı́az-Cabiale, Z., Rivera, A., Ferraro, L., Tanganelli, S., Tarakanov, A. O., Garriga, P., Narváez, J. Á., et al. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00136 · Cited by 73 · see citing works

ABP688, a novel selective and high affinity ligand for the labeling of mGlu5 receptors: Identification, in vitro pharmacology, pharmacokinetic and biodistribution studies

Hintermann, S., Vranesic, I., Allgeier, H., Bruelisauer, A., Hoyer, D., Lemaire, M., Moenius, T., Urwyler, S., Whitebread, S., Gasparini, F., et al. (2006) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2006.10.038 · Cited by 71 · see citing works

Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators: Discovery of 2-Chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1 <i>H</i> -imidazol-4-ylethynyl]pyridine (Basimglurant, RO4917523), a Promising Novel Medicine for Psychiatric Diseases

Jaeschke, G., Kolczewski, S., Spooren, W., Vieira, E., Bitter-Stoll, N., Boissin, P., Borroni, E., Büttelmann, B., Ceccarelli, S., Clemann, N., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm501642c · Cited by 66 · see citing works

Functional interaction of metabotropic glutamate receptor 5 and NMDA-receptor by a metabotropic glutamate receptor 5 positive allosteric modulator

Rosenbrock, H., Kramer, G., Hobson, S., Koroś, E., Grundl, M. A., Grauert, M., Reymann, K. G., & Schröder, U. H. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.02.057 · Cited by 62 · see citing works

The anxiolytic and analgesic properties of fenobam, a potent mGlu5 receptor antagonist, in relation to the impairment of learning

Jacob, W., Gravius, A., Pietraszek, M., Nagel, J., Владимировна, Б. И., Шекунова, Е. В., Malyshkin, A. A., Greco, S., Barberi, C., & Danysz, W. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.04.011 · Cited by 59 · see citing works

Metabotropic glutamate autoreceptors of the mGlu5 subtype positively modulate neuronal glutamate release in the rat forebrain in vitro

Thomas, L. S., Jane, D. E., Harris, J. R., & Croucher, M. J. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(99)00223-3 · Cited by 59 · see citing works

Allosteric modulation of metabotropic glutamate receptor 5 affects phosphorylation, internalization, and desensitization of the μ-opioid receptor

Schröder, H., Wu, D.-F., Seifert, A., Rankovic, M., Schulz, S., Höllt, V., & Koch, T. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.12.010 · Cited by 57 · see citing works

Effect of chronic imipramine or electroconvulsive shock on the expression of mGluR1a and mGluR5a immunoreactivity in rat brain hippocampus

Śmiałowska, M., Szewczyk, B., Brański, P., Wierońska, J. M., Pałucha-Poniewiera, A., Bajkowska, M., & Pilc, A. (2002) · Neuropharmacology · doi:10.1016/s0028-3908(02)00062-x · Cited by 56 · see citing works

Differential regulation of CaMK IIα interactions with m G luR5 and NMDA receptors by C a2+ in neurons

Jin, D., Guo, M., Xue, B., Mao, L., & Wang, J. Q. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12434 · Cited by 49 · see citing works

Evidence for the existence of FGFR1–5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system

Borroto‐Escuela, D. O., Narváez, M., Pérez‐Alea, M., Tarakanov, A. O., Jimenez‐Beristain, A., Mudò, G., Agnati, L. F., Ciruela, F., Belluardo, N., & Fuxé, K. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.11.112 · Cited by 47 · see citing works

Molecular Insights into Metabotropic Glutamate Receptor Allosteric Modulation

Gregory, K. J., & Conn, P. J. (2015) · Molecular Pharmacology · doi:10.1124/mol.114.097220 · Cited by 44 · see citing works

G-protein-coupled receptor type A heteromers as an emerging therapeutic target

Guidolin, D., Agnati, L. F., Marcoli, M., Borroto‐Escuela, D. O., & Fuxé, K. (2014) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.981155 · Cited by 43 · see citing works

Effect of MPEP treatment on brain-derived neurotrophic factor gene expression.

Legutko, B., Szewczyk, B., Pomierny-Chamioło, L., Nowak, G., & Pilc, A. (2006) · PubMed · Cited by 39 · see citing works

Metabotropic Glutamate Receptors as Therapeutic Targets for Cognitive Disorders

Gravius, A., Pietraszek, M., Dekundy, A., & Danysz, W. (2010) · Current Topics in Medicinal Chemistry · doi:10.2174/156802610790411018 · Cited by 39 · see citing works

Receptor-receptor interactions in heteroreceptor complexes: a new principle in biology. Focus on their role in learning and memory

Fuxé, K., Borroto-Escuela, D. O., Ciruela, F., Guidolin, D., & Agnati, L. F. (2014) · Neuroscience Discovery · doi:10.7243/2052-6946-2-6 · Cited by 38 · see citing works

Metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine produces antidepressant effects in rats: Role of brain-derived neurotrophic factor

Liu, C. Y., Jiang, X. X., Zhu, Y. H., & Wei, D. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.08.010 · Cited by 36 · see citing works

Mavoglurant as a treatment for Parkinson’s disease

Petrov, D., Pedrós, I., de Lemos, M. L., Pallàs, M., Canudas, A. M., Lazarowski, A., Beas‐Zárate, C., Auladell, C., Folch, J., & Camins, A. (2014) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.931370 · Cited by 36 · see citing works

Metabotropic Glutamate Receptor Enhancement of Spontaneous IPSCs in Neocortical Interneurons

Zhou, F.-M., & Hablitz, J. J. (1997) · Journal of Neurophysiology · doi:10.1152/jn.1997.78.5.2287 · Cited by 34 · see citing works

Neuroimaging and Physiological Evidence for Involvement of Glutamatergic Transmission in Regulation of the Striatal Dopaminergic System

Tokunaga, M., Seneca, N. M., Shin, R.-M., Maeda, J., Obayashi, S., Okauchi, T., Nagai, Y., Zhang, M., Nakao, R., Ito, H., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2559-08.2009 · Cited by 33 · see citing works

On the role of adenosine (A)2A receptors in cocaine-induced reward: a pharmacological and neurochemical analysis in rats

Wydra, K., Gołembiowska, K., Suder, A., Kamińska, K., Fuxé, K., & Filip, M. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3675-2 · Cited by 31 · see citing works

l-glutamate reduces the affinity of [3H]N-propylnorapomorphine binding sites in striatal membranes

Fuxé, K., Celani, M. F., Martire, M., Zini, I., Zoli, M., & Agnati, L. F. (1984) · European Journal of Pharmacology · doi:10.1016/0014-2999(84)90326-1 · Cited by 29 · see citing works

20 Years On

Glanville, J. (2009) · Index on Censorship · doi:10.1080/03064220903238112 · Cited by 26 · see citing works

The effects of the mGluR5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) on the stimulation of dopamine release evoked by nicotine in the rat brain

Tronci, V., & Balfour, D. J. K. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.12.024 · Cited by 25 · see citing works

mGlu5R promotes glutamate AMPA receptor phosphorylation via activation of PKA/DARPP-32 signaling in striatopallidal medium spiny neurons

Dell’Anno, M. T., Pallottino, S., & Fisone, G. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.03.025 · Cited by 24 · see citing works

Targeting Striatal Metabotropic Glutamate Receptor Type 5 in Parkinson`s Disease: Bridging Molecular Studies and Clinical Trials

Vallano, A., Fernández‐Dueñas, V., García-Negredo, G., Quijada-Manuitt, M. Á., Simon, C. P., Cuffí, M. L., Carbonell, L., Sánchez, S., Arnau, J. M., & Ciruela, F. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/18715273113129990115 · Cited by 13 · see citing works

Glutamatergic mechanisms in antidepressant treatments

Marek, G. J. (2002) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(02)80124-9 · Cited by 4 · see citing works

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

Howard, D. M., Adams, M. J., Clarke, T.-K., Hafferty, J. D., Gibson, J., Shirali, M., Coleman, J. R. I., Hagenaars, S. P., Ward, J., Wigmore, E. M., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0326-7 · Cited by 2,565 · see citing works

Glutamate and Gamma-Aminobutyric Acid Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine

Lener, M. S., Niciu, M. J., Ballard, E. D., Park, M., Park, L. T., Nugent, A. C., & Zarate, C. A. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.005 · Cited by 468 · see citing works

GPCR drug discovery: new agents, targets and indications

Lorente, J. S., Sokolov, A. V., Ferguson, G., Schiöth, H. B., Hauser, A. S., & Gloriam, D. E. I. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01139-y · Cited by 274 · see citing works

Pathophysiology and Current Drug Treatments for Post-Stroke Depression: A Review

Frank, D., Gruenbaum, B. F., Zlotnik, A. A., Semyonov, M., Frenkel, A., & Boyko, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315114 · Cited by 154 · see citing works

Understanding the Role of GPCR Heteroreceptor Complexes in Modulating the Brain Networks in Health and Disease

Borroto‐Escuela, D. O., Carlsson, J., Ambrogini, P., Narváez, M., Wydra, K., Tarakanov, A. O., Li, X., Millón, C., Ferraro, L., Cuppini, R., et al. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00037 · Cited by 375 · see citing works

Structure-Based Optimization Strategies for G Protein-Coupled Receptor (GPCR) Allosteric Modulators: A Case Study from Analyses of New Metabotropic Glutamate Receptor 5 (mGlu 5 ) X-ray Structures

Christopher, J. A., Orgován, Z., Congreve, M., Dore, A. S., Errey, J. C., Marshall, F. H., Mason, J. S., Okrasa, K., Rucktooa, P., Serrano‐Vega, M. J., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01722 · Cited by 91 · see citing works

mGlu5negative allosteric modulators: a patent review (2013 - 2016)

Emmitte, K. A. (2017) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2017.1280466 · Cited by 76 · see citing works

Upregulation of prefrontal metabotropic glutamate receptor 5 mediates neuropathic pain and negative mood symptoms after spinal nerve injury in rats

Chung, G., Kim, C. Y., Yun, Y.-C., Yoon, S. H., Kim, M., Kim, Y. K., & Kim, S. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-09991-8 · Cited by 65 · see citing works

Brain Dopamine Transmission in Health and Parkinson's Disease: Modulation of Synaptic Transmission and Plasticity Through Volume Transmission and Dopamine Heteroreceptors

Borroto‐Escuela, D. O., de la Mora, M. P., Manger, P. R., Narváez, M., Beggiato, S., Crespo‐Ramírez, M., Navarro, G., Wydra, K., Dı́az-Cabiale, Z., Rivera, A., et al. (2018) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2018.00020 · Cited by 61 · see citing works

FGFR1–5-HT1A Heteroreceptor Complexes: Implications for Understanding and Treating Major Depression

Borroto‐Escuela, D. O., Tarakanov, A. O., & Fuxé, K. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.11.003 · Cited by 50 · see citing works

Glutamate heteroreceptor complexes in the brain

Borroto‐Escuela, D. O., Tarakanov, A. O., Brito, I., & Fuxé, K. (2018) · Pharmacological Reports · doi:10.1016/j.pharep.2018.04.002 · Cited by 42 · see citing works

Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?

Budgett, R. F., Bakker, G., Sergeev, E., Bennett, K. A., & Bradley, S. J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.893422 · Cited by 38 · see citing works

Mechanisms of Skin Toxicity Associated with Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.

Shah, F., Stepan, A., O'Mahony, A., Velichko, S., Folias, A. E., Houle, C., Shaffer, C. L., Marcek, J., Whritenour, J., Stanton, R., et al. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.06.003 · Cited by 29 · see citing works

Subtype-selective mechanisms of negative allosteric modulators binding to group I metabotropic glutamate receptors

Fu, T., Tu, G., Ping, M., Zheng, G., Yang, F., Yang, H. J., Zhang, Y., Yao, X., Xue, W., & Zhu, F. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00541-z · Cited by 36 · see citing works

Discovery of N -(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation

Felts, A. S., Rodriguez, A. L., Blobaum, A. L., Morrison, R. D., Bates, B. S., Gray, A. T., Rook, J. M., Tantawy, M. N., Byers, F. W., Chang, S., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00410 · Cited by 34 · see citing works

Investigational drugs for treating major depressive disorder

Dhir, A. (2016) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1267727 · Cited by 31 · see citing works

Beyond serotonin: newer antidepressants in the future

Rakesh, G., Pae, C., & Masand, P. S. (2017) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2017.1341310 · Cited by 25 · see citing works

G Protein-Coupled Receptor Heteromers as Putative Pharmacotherapeutic Targets in Autism

DelaCuesta-Barrutia, J., Peñagarikano, O., & Erdozain, A. M. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.588662 · Cited by 18 · see citing works

Blocking metabotropic glutamate receptor subtype 5 relieves maladaptive chronic stress consequences

Peterlik, D., Stangl, C., Bauer, A., Bludau, A., Keller, J., Grabski, D., Killian, T., Schmidt, D., Zajicek, F., Jaeschke, G., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.08.007 · Cited by 18 · see citing works

Structure-based discovery and development of metabotropic glutamate receptor 5 negative allosteric modulators

Bennett, K. A., Christopher, J. A., & Tehan, B. G. (2020) · Advances in pharmacology · doi:10.1016/bs.apha.2020.03.001 · Cited by 14 · see citing works

Drugs with glutamate-based mechanisms of action in psychiatry

Chrobak, A. A., & Siwek, M. (2024) · Pharmacological Reports · doi:10.1007/s43440-024-00656-8 · Cited by 14 · see citing works

Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors

del Torrent, C. L., Pérez‐Benito, L., & Tresadern, G. (2019) · Molecules · doi:10.3390/molecules24061098 · Cited by 13 · see citing works

A molecular perspective on mGluR5 regulation in the antidepressant effect of ketamine

Elmeseiny, O. S. A., & Müller, H. K. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107081 · Cited by 14 · see citing works

Current Trends in Identifying Rapidly Acting Treatments for Depression

Ionescu, D., & Papakostas, G. (2016) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-016-0075-4 · Cited by 13 · see citing works

Metabotropic Glutamate Receptor 5 in the Medial Prefrontal Cortex as a Molecular Determinant of Pain and Ensuing Depression

Chung, G., Kim, S. J., & Kim, S. K. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00376 · Cited by 12 · see citing works

Beyond monoamines: II. Novel applications for PET imaging in psychiatric disorders

Royse, S. K., Lopresti, B. J., Mathis, C. A., Tollefson, S., & Narendran, R. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15657 · Cited by 10 · see citing works

Discovery and Characterization of (R)-6-Neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (PF-06462894), an Alkyne-Lacking Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator Profiled in both Rat and Nonhuman Primates

Stepan, A. F., Claffey, M. M., Reese, M. R., Balan, G., Barreiro, G., Barricklow, J., Bohanon, M. J., Boscoe, B. P., Cappon, G. D., Chenard, L. K., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00604 · Cited by 9 · see citing works

Current Advances in the Synthesis and Biological Evaluation of Pharmacologically Relevant 1,2,4,5-Tetrasubstituted-1H-Imidazole Derivatives

Rossi, R., & Ciofalo, M. (2019) · Current Organic Chemistry · doi:10.2174/1385272823666191014154129 · Cited by 8 · see citing works

Analysis of the Gut Microbiota and Inflammatory Factors in mGluR5-Knockout Mice

Cai, G., Zhu, Y., Chen, J., Zhao, S., Wang, L., Wang, M., Huang, J., & Wu, S. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00335 · Cited by 5 · see citing works

Depression-like effects induced by chronic unpredictable mild stress in mice are rapidly reversed by a partial negative allosteric modulator of mGlu5 receptor, M-5MPEP

Pałucha-Poniewiera, A., Bobula, B., Rafało-Ulińska, A., & Kaczorowska, K. (2024) · Psychopharmacology · doi:10.1007/s00213-024-06724-4 · Cited by 5 · see citing works

Combining In Vivo and Organotypic In Vitro Approaches to Assess the Human Relevance of Basimglurant (RG7090), a Potential CAR Activator

Nudischer, R., Renggli, K., Bertinetti‐Lapatki, C., Hoflack, J.-C., Flint, N. A., Sewing, S., Pedersen, L., Schadt, S., Higgins, L. G., Vardy, A., et al. (2020) · Toxicological Sciences · doi:10.1093/toxsci/kfaa076 · Cited by 4 · see citing works

G protein-coupled receptors in drug discovery for neurological and psychiatric disorders: therapeutic targets, mechanisms, and future prospects

Zhang, M., Rehman, M. U., & Long, S. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117380 · Cited by 4 · see citing works

Glutamate receptors as regulators of synaptic plasticity in neuropsychiatric disorders: pathological insight and translational perspectives

Srivastava, J., Yadav, J., & Dubey, N. (2026) · Cognitive Neurodynamics · doi:10.1007/s11571-026-10446-y · Cited by 3 · see citing works

Modulating Neuroplasticity: Lessons Learned from Antidepressants and Emerging Novel Therapeutics

Yates, C. G., Kruse, J. L., Price, J. B., Robertson, A. A. B., & Tye, S. J. (2021) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-021-00249-9 · Cited by 3 · see citing works

Metabotropic glutamate receptor 5 in depression: Mechanisms and therapeutic potential

He, C., Zhang, J., Wang, J., Zhu, G., & Yang, S. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117976 · Cited by 3 · see citing works

Repeated episodes of transient reduction of oxygen exposure simulating aircraft cabin conditions enhance resilience to stress in mice

Ginerete, R. P., Mascio, G., Liberatore, F., Bucci, D., Antenucci, N., Pietro, P. D., Cannella, M., Imbriglio, T., Notartomaso, S., Nicoletti, F., et al. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15495 · Cited by 2 · see citing works

Modulation of Metabotropic Glutamate Receptors as a Strategy to Improve the Efficacy and Safety of Ketamine as an Antidepressant

Pałucha-Poniewiera, A. (2025) · Cells · doi:10.3390/cells14241967 · Cited by 1 · see citing works

Chronic Pain and Major Depression: Shared Psychological and Neurobiological Mechanism

Lee, S.-H., & Kim, Y. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-981-95-6872-7_9 · Cited by 2 · see citing works

Overlapping Chronic Pain and Depression: Pathophysiology and Management

Jaracz, J. (2017) · Springer eBooks · doi:10.1007/978-981-10-6577-4_12 · Cited by 1 · see citing works

Homology modeling and molecular docking study of metabotropic glutamate receptor 5 variant F: an attempt to develop drugs for treating CNS diseases

Ahmad, N., Khan, K., Rashid, H. U., Khan, S. W., Umar, M. N., Gulfam, N., Zahoor, M., Ullah, R., & Ali, E. A. (2024) · Zeitschrift für Physikalische Chemie · doi:10.1515/zpch-2023-0449 · Cited by 1 · see citing works

(R)-ketamine induces mGlu5 receptor-dependent antidepressant-like effects in the chronic unpredictable mild stress model of depression in mice

Pałucha-Poniewiera, A., Rafało-Ulińska, A., Faron‐Górecka, A., Pabian, P., & Kaczorowska, K. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06803-0 · Cited by 1 · see citing works

Novel Antidepressant Approaches for Refractory Depression

Postorivo, D., & Tye, S. J. (2021) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-021-00246-y · Cited by 1 · see citing works

Depression and musculoskeletal diseases: a framework of systemic mechanisms

Yang, X., Zhao, Y., Gao, W., Liu, J., Wang, T., Wang, J., & 王飞雪 (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1977499

BindingDB Entry 50000654: Discovery of N-(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation.

BindingDB (2019) · UC San Diego · doi:10.7270/q2jh3pm7

BindingDB Entry 50000125: Discovery and Characterization of (R)-6-Neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (PF-06462894), an Alkyne-Lacking Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator Profiled in both Rat and Nonhuman Primates.

BindingDB (2019) · UC San Diego · doi:10.7270/q2dj5hs8

Pharmacology of Basimglurant (RO4917523, RG7090), a Unique Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator in Clinical Development for Depression

Lindemann, L., Porter, R. H., Scharf, S. H., Kuennecke, B., Bruns, A., von Kienlin, M., Harrison, A. C., Paehler, A., Funk, C., Gloge, A., et al. (2015) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.222463 · Cited by 107 · see citing works

Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators: Discovery of 2-Chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1 <i>H</i> -imidazol-4-ylethynyl]pyridine (Basimglurant, RO4917523), a Promising Novel Medicine for Psychiatric Diseases

Jaeschke, G., Kolczewski, S., Spooren, W., Vieira, E., Bitter-Stoll, N., Boissin, P., Borroni, E., Büttelmann, B., Ceccarelli, S., Clemann, N., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm501642c · Cited by 66 · see citing works

Metabotropic glutamate receptor 5 in depression: Mechanisms and therapeutic potential

He, C., Zhang, J., Wang, J., Zhu, G., & Yang, S. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117976 · Cited by 3 · see citing works

T1. THE ANTIDEPRESSANT ACTIVITY OF BASIMGLURANT, A NOVEL MGLU5-NAM; A RANDOMIZED, DOUBLE-BLIND, PLACEBO- CONTROLLED STUDY IN THE ADJUNCTIVE TREATMENT OF MDD

Quiroz, J. A., Deptula, D., Banken, L., Beyer, U., & da Fontoura, P. P. (2015)

Allosteric Modulation of Metabotropic Glutamate Receptor 5 (Mglur5) In Treatment-Resistant Depression: Electrophysiological and Behavioral Correlates in Rodent Models

Faizan Hussain*, S. K. (2026) · Journal of Pharmaceutical Sciences · doi:10.5281/zenodo.18645541