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.

Article Details

Citation

Grunder G, Yokoi F, Offord SJ, Ravert HT, Dannals RF, Salzmann JK, Szymanski S, Wilson PD, Howard DR, Wong DF

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.

Neuropsychopharmacology. 1997 Sep;17(3):175-85. doi: 10.1016/S0893-133X(97)00044-4.

PubMed ID
9272484 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Volinanserin5-hydroxytryptamine receptor 2AProteinHumans
Unknown
Antagonist
Details