A radiolabeled agonist tracer, (11)C-CIMBI-5, was developed for PET imaging of the serotonin 2A (5-HT2A) receptor in the brain. In vitro assays showed CIMBI-5 is a high-affinity agonist at the 5-HT2A receptor. Ex vivo rat studies demonstrated a specific binding ratio of 0.77 ± 0.07 in the frontal cortex, which was reduced to cerebellar levels after ketanserin treatment, indicating selective binding. PET studies in pigs revealed a cortical binding potential of 0.46 ± 0.12 and a target-to-background ratio similar to the antagonist tracer (18)F-altanserin. Ketanserin treatment reduced cortical binding to cerebellar levels, confirming selective in vivo binding. (11)C-CIMBI-5 is a promising tool for investigating 5-HT2A agonist binding in the living human brain.
The metabolism of the potent psychedelic compound 25B-NBOMe, an illicit drug linked to several fatalities, was studied in pigs and humans. The primary metabolic pathway is 5'-demethylation, followed by conjugation to glucuronic acid. These findings were confirmed by carbon-11 labeling of 25B-NBOMe in three different positions and in vivo evaluation in both species.
Ketanserin, a drug that blocks the serotonin 2A (5-HT2A) receptor, occupies this receptor in the human brain in a dose-dependent manner. In a positron emission tomography (PET) study with healthy participants, oral doses of 10, 20, or 40 mg of ketanserin led to a plasma concentration-related increase in receptor occupancy. The half-maximal effective concentration (EC50) was 2.52 ng/mL, corresponding to about a 10 mg oral dose. These findings clarify how ketanserin works in the brain, aiding its use as a research tool and suggesting potential for treating bad psychedelic experiences.