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
2000
Kinetic Analysis of the 5-HT2A Ligand [11C]MDL 100,907
Watabe H, Channing M, Der M, Adams H, Jagoda E, Herscovitch P, Eckelman W, Carson R. Kinetic Analysis of the 5-HT2A Ligand [11C]MDL 100,907. Cerebrovascular And Brain Metabolism Reviews 2000, 20: 899-909. PMID: 10894173, DOI: 10.1097/00004647-200006000-00002.Peer-Reviewed Original ResearchThe Suitability of [11C]-α-Methyl-L-tryptophan as a Tracer for Serotonin Synthesis: Studies With Dual Administration of [11C] and [14C] Labeled Tracer
Shoaf S, Carson R, Hommer D, Williams W, Higley J, Schmall B, Herscovitch P, Eckelman W, Linnoila M. The Suitability of [11C]-α-Methyl-L-tryptophan as a Tracer for Serotonin Synthesis: Studies With Dual Administration of [11C] and [14C] Labeled Tracer. Cerebrovascular And Brain Metabolism Reviews 2000, 20: 244-252. PMID: 10698060, DOI: 10.1097/00004647-200002000-00004.Peer-Reviewed Original ResearchConceptsPositron emission tomographySerotonin synthesisOverdose of phenobarbitalBrain serotonin synthesis rateIsoflurane-anesthetized rhesus monkeysSerotonin synthesis rateBrain concentrationsSecond doseBrain samplesEmission tomographyRhesus monkeysDual administrationTryptophan uptakePatlak plotSerotoninMinimal conversionAdministrationMonkeysSynthesis rateL-tryptophanPET imagesPET dataTotal countOverdoseExternal quantification