title: Time course of 5-HT2A receptor occupancy in the human brain after a single oral dose of the putative antipsychotic drug MDL 100,907 measured by positron emission tomography.
abstract: MDL 100,907 is a potent and selective antagonist of 5-HT2A serotonin receptors. Animals studies suggest that MDL 100,907 may behave as an atypical antipsychotic drug. Positron emission tomograph (PET) using [11C]NMSP as the radiotracer was used to define the time course of 5-HT2 receptor occupancy in the human frontal cerebral cortex after a single oral dose of MDL 100,907 (10 or 20 mg) in nine healthy subjects. After the baseline scan each subject was studied three times post dosing at various time points. 5-HT2 occupancies were in the range of 70 and 90% after each dose. While the occupancy remains in this range over 24 hours after 20 mg MDL 100,907, it decreases by about 20% at 24 hours compared to the timepoint at 8 hours, when only 10 mg are administered (p < 0.05). Our results should allow determination of the appropriate dosing regimen for future trials in schizophrenic patients.
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287-0807, USA.
authors.forename: G
authors.initials: G
authors.lastname: Gründer
authors.forename: F
authors.initials: F
authors.lastname: Yokoi
authors.forename: S J
authors.initials: SJ
authors.lastname: Offord
authors.forename: H T
authors.initials: HT
authors.lastname: Ravert
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
authors.forename: J K
authors.initials: JK
authors.lastname: Salzmann
authors.forename: S
authors.initials: S
authors.lastname: Szymanski
authors.forename: P D
authors.initials: PD
authors.lastname: Wilson
authors.forename: D R
authors.initials: DR
authors.lastname: Howard
authors.forename: D F
authors.initials: DF
authors.lastname: Wong
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives; D013997:Time Factors; D014055:Tomography, Emission-Computed
chemical_list: D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D005464:Fluorobenzenes; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013134:Spiperone; C039167:3-N-methylspiperone; C079049:volinanserin