title: Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression.
abstract: Major depressive disorder (MDD) is a serious public health burden and a leading cause of disability. Its pharmacotherapy is currently limited to modulators of monoamine neurotransmitters and second-generation antipsychotics. Recently, glutamatergic approaches for the treatment of MDD have increasingly received attention, and preclinical research suggests that metabotropic glutamate receptor 5 (mGlu5) inhibitors have antidepressant-like properties. Basimglurant (2-chloro-4-[1-(4-fluoro-phenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]-pyridine) is a novel mGlu5 negative allosteric modulator currently in phase 2 clinical development for MDD and fragile X syndrome. Here, the comprehensive preclinical pharmacological profile of basimglurant is presented with a focus on its therapeutic potential for MDD and drug-like properties. Basimglurant is a potent, selective, and safe mGlu5 inhibitor with good oral bioavailability and long half-life supportive of once-daily administration, good brain penetration, and high in vivo potency. It has antidepressant properties that are corroborated by its functional magnetic imaging profile as well as anxiolytic-like and antinociceptive features. In electroencephalography recordings, basimglurant shows wake-promoting effects followed by increased delta power during subsequent non-rapid eye movement sleep. In microdialysis studies, basimglurant had no effect on monoamine transmitter levels in the frontal cortex or nucleus accumbens except for a moderate increase of accumbal dopamine, which is in line with its lack of pharmacological activity on monoamine reuptake transporters. These data taken together, basimglurant has favorable drug-like properties, a differentiated molecular mechanism of action, and antidepressant-like features that suggest the possibility of also addressing important comorbidities of MDD including anxiety and pain as well as daytime sleepiness and apathy or lethargy.
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.) lothar.lindemann@roche.com.
authors: Lothar
authors: L
authors: Lindemann
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Richard H
authors: RH
authors: Porter
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Sebastian H
authors: SH
authors: Scharf
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Basil
authors: B
authors: Kuennecke
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Andreas
authors: A
authors: Bruns
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Markus
authors: M
authors: von Kienlin
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Anthony C
authors: AC
authors: Harrison
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Axel
authors: A
authors: Paehler
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Christoph
authors: C
authors: Funk
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Andreas
authors: A
authors: Gloge
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Manfred
authors: M
authors: Schneider
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Neil J
authors: NJ
authors: Parrott
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Liudmila
authors: L
authors: Polonchuk
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Urs
authors: U
authors: Niederhauser
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Stephen R
authors: SR
authors: Morairty
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Thomas S
authors: TS
authors: Kilduff
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Eric
authors: E
authors: Vieira
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Sabine
authors: S
authors: Kolczewski
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Juergen
authors: J
authors: Wichmann
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Thomas
authors: T
authors: Hartung
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Michael
authors: M
authors: Honer
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Edilio
authors: E
authors: Borroni
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Jean-Luc
authors: JL
authors: Moreau
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Eric
authors: E
authors: Prinssen
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Will
authors: W
authors: Spooren
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Joseph G
authors: JG
authors: Wettstein
authors: Roche Pharmaceutical Research and Early Development, Discovery Neuroscience, Neuroscience, Ophthalmology, and Rare Diseases (L.L., S.H.S., B.K., A.B., M.v.K., M.H., E.B., E.P., W.S., J.G.W.), Discovery Chemistry (E.V., S.K., J.W., G.J.), Operations for Neuroscience, Ophthalmology, and Rare Diseases (R.H.P., J.-L.M.), Pharmaceutical Sciences (A.C.H., A.P., C.F., A.G., M.S., N.J.P., L.P., U.N.), and Small Molecules Process Research and Synthesis (T.H.), Roche Innovation Center Basel, Basel, Switzerland; and Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California (S.R.M., T.S.K.).
authors: Georg
authors: G
authors: Jaeschke
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D003412:Cricetulus; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D054314:Drug Inverse Agonism; D004569:Electroencephalography; D005260:Female; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011869:Radioligand Assay; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000503:physiopathology
chemical_list: C000596770:2-chloro-4-(1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl)pyridine; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D007093:Imidazoles; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5