2024
PET imaging of M4 muscarinic acetylcholine receptors in rhesus macaques using [11C]MK-6884: Quantification with kinetic modeling and receptor occupancy by CVL-231 (emraclidine), a novel positive allosteric modulator
Belov V, Guehl N, Duvvuri S, Iredale P, Moon S, Dhaynaut M, Chakilam S, MacDonagh A, Rice P, Yokell D, Renger J, Fakhri G, Normandin M. PET imaging of M4 muscarinic acetylcholine receptors in rhesus macaques using [11C]MK-6884: Quantification with kinetic modeling and receptor occupancy by CVL-231 (emraclidine), a novel positive allosteric modulator. Cerebrovascular And Brain Metabolism Reviews 2024, 44: 1329-1342. PMID: 38477292, PMCID: PMC11342722, DOI: 10.1177/0271678x241238820.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsReceptor occupancyNon-human primatesBinding potentialPositron emission tomographyMuscarinic acetylcholine receptorsAllosteric modulatorsNon-human primate brainM4 muscarinic acetylcholine receptorStriatal hyperdopaminergiaAcetylcholine receptorsBrain regionsCaudate nucleusTotal volume of distributionDose-dependent blockReference regionVolume of distributionPositron emission tomography imagingEmission tomographyReceptor levelsFunction of dosePET scansClinical trialsBlood-basedRhesus macaques
2022
Synthesis and Characterization of 5‑(2-Fluoro-4‑[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro‑2H‑pyrano[2,3‑b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Dhaynaut M, Lan Y, Guehl N, Huynh D, Iyengar S, Afshar S, Jain M, Pickett J, Kang H, Wang H, Moon S, Ondrechen M, Wang C, Shoup T, Fakhri G, Normandin M, Brownell A. Synthesis and Characterization of 5‑(2-Fluoro-4‑[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro‑2H‑pyrano[2,3‑b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Journal Of Medicinal Chemistry 2022, 65: 2593-2609. PMID: 35089713, PMCID: PMC9434702, DOI: 10.1021/acs.jmedchem.1c02004.Peer-Reviewed Original ResearchConceptsNegative allosteric modulatorsMetabotropic glutamate receptor 2Positron emission tomographyGlutamate receptor 2MGluR2 functionNeuropsychiatric disordersDrug effectsBrain heterogeneityReceptor 2Allosteric modulatorsMGluR2Nonhuman primatesBrain imagingPositron emission tomography imagingPositron emission tomography imaging ligandsHigh molar activityEmission tomographyExcellent radiochemical purityImaging ligandsBlocking agentsPET imagingMolar activityTherapeutic targetMetabotropicDisorders