The selective 5-HT2A receptor agonist 25CN-NBOH: structure-activity relationship, in vivo pharmacology, and in vitro and ex vivo binding characteristics of [3H]25CN-NBOH.
Biochemical Pharmacology April 13, 2020 A. Jensen, A. Halberstadt, Emil Märcher-Rørsted et al. 25 citations
Modifications to specific positions on the 25CN-NBOH molecule, a highly selective 5-HT2A receptor agonist, can retain or reduce its activity. Six new analogs were tested; 3′-methyl and fused-ring variants kept high 5-HT2A receptor activity, while 3′-methoxy and 3′-ethyl versions lost binding and potency. All six analogs showed only partial agonism or antagonism. In mice, 25CN-NBOH and a close analog triggered head-twitch responses (a hallmark of 5-HT2A activation) and reduced marble-burying behavior, suggesting potential benefits for cognitive rigidity disorders. A tritium-labeled version of 25CN-NBOH showed high binding affinity and selectivity for 5-HT2A receptors in rat brain tissue, providing a new tool for future receptor studies.