Investigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans
Sawant‐Basak A, Chen L, Lockwood P, Boyden T, Doran A, Mancuso J, Zasadny K, McCarthy T, Morris E, Carson R, Esterlis I, Huang Y, Nabulsi N, Planeta B, Fullerton T. Investigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans. Biopharmaceutics & Drug Disposition 2023, 44: 48-59. PMID: 36825693, DOI: 10.1002/bdd.2351.Peer-Reviewed Original ResearchConceptsNon-human primatesBrain penetrationPositron emission tomographyReceptor occupancyUnbound concentrationsPre-clinical evidenceVivo brain penetrationConcentration-dependent increaseP-glycoprotein substratesPlasma ECsP-gpAlzheimer's diseaseEmission tomographyRat BBBTarget engagementCumulative evidenceDependent increaseTransporter substratesCNS distributionBBBRatsDiseasePrimatesSpecies differencesHumansExamining mGlu5 Receptor Availability as a Predictor of Vulnerability to PTSD: An [18F]FPEB and PET Study in Male and Female Rats
Asch R, Fowles K, Pietrzak R, Taylor J, Esterlis I. Examining mGlu5 Receptor Availability as a Predictor of Vulnerability to PTSD: An [18F]FPEB and PET Study in Male and Female Rats. Chronic Stress 2023, 7: 24705470231215001. PMID: 38024327, PMCID: PMC10666551, DOI: 10.1177/24705470231215001.Peer-Reviewed Original ResearchPost-traumatic stress disorderReceptor availabilityFemale ratsPathophysiology of PTSDFootshock exposureMetabotropic glutamate receptor 5Recent preclinical findingsGlutamate receptor 5Positron emission tomographyPreclinical findingsClinical findingsFe ratsReceptor 5Lower baselineEmission tomographyGreater riskPET studiesRatsStress disorderDifferential involvementPassive copingSex differencesMalesPTSD susceptibilityBaseline