The Selective 5HT2A Receptor Agonist, 25CN-NBOH Exerts Excitatory and Inhibitory Cellular Actions on Mouse Medial Prefrontal Cortical Neurons.
Synapse (New York, N.Y.) March 1, 2025 Yang Wang, Jesper L Kristensen, Kristi A Kohlmeier 5 citations
The synthetic psychedelic 25CN-NBOH, which binds strongly to serotonin type 2A receptors, has a dual effect on neurons in the mouse medial prefrontal cortex. Acute application of a high concentration (10 µM) increased the frequency of spontaneous excitatory postsynaptic currents, an effect dependent on serotonin 2A receptor activation and not seen with chronic exposure or a lower concentration (200 nM). However, both concentrations suppressed the firing rate of pyramidal neurons after acute and one-hour exposure. This suppression was independent of serotonin 2A receptors but mediated by M-current channels, as blocking M-currents reversed it. The compound thus enhances excitatory transmission while reducing overall excitability, revealing complex cellular actions that may underlie its therapeutic effects.