Neurochemical characterization of 5-HT 2A R partial agonists with simultaneous PET-MRI
Journal of Cerebral Blood Flow & Metabolism November 29, 2024 Frederick A. Bagdasarian, Kristian Larsen, Deng Hong et al. 1 citation
Psilocybin, lisuride, and 25CN-NBOH, three serotonin 2A receptor agonists with different pharmacological profiles, produce distinct brain blood flow patterns in anesthetized nonhuman primates. Psilocybin and lisuride, which are mixed partial agonists, caused biphasic cerebral blood volume changes, while the selective agonist 25CN-NBOH produced monophasic increases. Cortical receptor occupancy for psilocybin plateaued at 60 µg/kg (32%), similar to that of a lower dose of lisuride (31%). 25CN-NBOH had lower occupancy (7%) but larger blood volume changes. The relationship between blood volume and receptor occupancy appeared linear for lisuride and 25CN-NBOH but not for psilocybin. These differences may stem from the mixed affinity profiles of the agonists, providing insights for developing psychiatric therapeutics.