CGS-12066, also known as CGS-12066A and CGS-12066B, is a predominant serotonin 5-HT<sub>1B</sub> receptor agonist which was under development for the treatment of anxiety disorders but was never marketed. Its route of administration is unknown.
In terms of affinity, it is moderately (17-fold) selective for the serotonin 5-HT<sub>1B</sub> receptor over the serotonin 5-HT<sub>1A</sub> receptor, where it is also an agonist. Although reported to be a selective serotonin 5-HT<sub>1B</sub> receptor agonist, it was subsequently found to be equipotent as an agonist of the serotonin 5-HT<sub>1B</sub> and 5-HT<sub>1D</sub> receptors. The drug showed weak affinity for the serotonin 5-HT<sub>2A</sub>, 5-HT<sub>2B</sub>, and 5-HT<sub>2C</sub> receptors (K<sub>i</sub> = 871âÂÂ4,270nM). It had minimal affinity for various adrenergic and dopamine receptors.
CGS-12066 produces anxiolytic-like, prosocial, and antiaggressive effects in rodents. There is rapid tolerance to its prosocial effects, thought to be due to desensitization of serotonin 5-HT<sub>1B</sub> receptors. The drug also produces hyperlocomotion in rodents, although to a much lesser extent than RU-24969, perhaps due to its lower-efficacy partial agonism of the serotonin 5-HT<sub>1B</sub> receptor. It produces wakefulness and reduces slow wave sleep (SWS) and rapid eye movement (REM) sleep in rodents. Some of the effects of CGS-12066 in animals, such as hypothermia and serotonin behavioral syndrome, are not mediated by the serotonin 5-HT<sub>1B</sub> receptor.
CGS-12066 was first described in the scientific literature by 1987. It reached the preclinical research stage of development for anxiety disorders prior to the discontinuation of its development in 1995.