ORG-12962 is a serotonin 5-HT<sub>2</sub> receptor agonist of the pyridinylpiperazine family which was under development for the treatment of major depressive disorder but was never marketed.
It acts preferentially as a partial agonist of the serotonin 5-HT<sub>2C</sub> receptor (K<sub>i</sub> = 12nM; = 97.7nM; = 62%). However, to a lesser extent, it is also a partial agonist of the serotonin 5-HT<sub>2A</sub> receptor (K<sub>i</sub> = 65nM; = 417nM; = 54%) and of the serotonin 5-HT<sub>2B</sub> receptor ( = 525nM; = 41%). In addition, ORG-12962 shows affinity for other serotonin receptors, such as the serotonin 5-HT<sub>1B</sub> receptor (K<sub>i</sub> = 100nM) and to a much lesser extent the serotonin 5-HT<sub>1A</sub> receptor (K<sub>i</sub> = 2,500nM).
In addition to depression, it was studied as a potential anxiolytic, but was discontinued from human trials after tests in a public speaking challenge showed that its anti-anxiety effects were accompanied by side effects such as dizziness and a "spacey" feeling, which were attributed as being possibly due to poor selectivity in vivo over the hallucinogenic serotonin 5-HT<sub>2A</sub> receptor.
ORG-12962 was first described in the scientific literature by 1995. It was developed by Organon. The drug reached phase 2 clinical trials for depression prior to the discontinuation of its development.