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

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 17; no. 3; pp. 175 - 185
• Main Authors: Gründer, M.D, Gerhard, Yokoi, M.D, Fuji, Offord, Ph.D, Steve J., Ravert, Ph.D, Hayden T., Dannals, Ph.D, Robert F., Salzmann, M.S, Joanne K., Szymanski, D.O, Sally, Wilson, Ph.D, P.David, Howard, Ph.D, Daniel R., Wong, M.D., Ph.D, Dean F.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-09-1997; Nature Publishing
• Subjects: 5-HT2 receptors; Adult; Antipsychotic Agents - metabolism; Antipsychotic drugs; Biological and medical sciences; Brain - metabolism; Carbon Radioisotopes; Female; Fluorobenzenes - administration & dosage; Fluorobenzenes - blood; Fluorobenzenes - metabolism; Human; Humans; Male; MDL 100,907; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Piperidines - administration & dosage; Piperidines - blood; Piperidines - metabolism; Positron Emission Tomography; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin - metabolism; Serotonin Antagonists - administration & dosage; Serotonin Antagonists - metabolism; Spiperone - analogs & derivatives; Time Factors; Tomography, Emission-Computed; Human; Antipsychotic drugs; 5-HT2 receptors; Positron Emission Tomography; MDL 100,907; Radionuclide study; Biological fixation; Neuroleptic; Psychotropic; Single dose; 5-HT2 receptor; Oral administration; Tomography; Mechanism of action; Normal; Emission tomography
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(97)00044-4

MDL 100,907 is a potent and selective antagonist of 5-HT2A serotonin receptors. Animal 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. [