2023
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 differencesHumans
2021
Low-Dose Augmentation With Buprenorphine for Treatment-Resistant Depression: A Multisite Randomized Controlled Trial With Multimodal Assessment of Target Engagement
Lee H, Blumberger D, Lenze E, Anderson S, Barch D, Black K, Cristancho P, Daskalakis Z, Eisenstein S, Huang Y, Li S, Lissemore J, McConathy J, Mulsant B, Rajji T, Reynolds C, Su Y, Tu Z, Voineskos D, Karp J. Low-Dose Augmentation With Buprenorphine for Treatment-Resistant Depression: A Multisite Randomized Controlled Trial With Multimodal Assessment of Target Engagement. Biological Psychiatry Global Open Science 2021, 2: 127-135. PMID: 36325158, PMCID: PMC9616305, DOI: 10.1016/j.bpsgos.2021.09.003.Peer-Reviewed Original ResearchTranscranial magnetic stimulation measuresTreatment-resistant depressionPositron emission tomographyFunctional magnetic resonanceTarget engagementClinical trialsCortical transmissionMontgomery-Åsberg Depression Rating ScalePlacebo-controlled clinical trialEmission tomographyLow-dose augmentationVenlafaxine extended releasePrimary outcome measureBlood oxygen level-dependent (BOLD) responseMajor depressive episodeDepression Rating ScaleExperimental therapeutic approachesYears of ageMultimodal assessmentLevel-dependent responsesMonetary incentive delay taskBrain positron emission tomographyPlacebo groupIncentive delay taskClinical effects