PNU-22394
chemical compound
PNU-22394, or PNU-22394A, also known as U-22394A, as well as 6-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole, is a serotonin 5-HT2 receptor agonist of the ibogalog family which was studied as an appetite suppressant and antipsychotic but was never marketed. As an ibogalog, PNU-22394 is a cyclized tryptamine and a simplified ibogaine analogue.
Pharmacology
PNU-22394 acts as a potent modulator of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. Its affinities (Ki), activational potencies (EC50Tooltip half-maximal effective concentration), and efficacies (EmaxTooltip maximal efficacy) were respectively 19 nM and 67.2 nM (64%) at the serotonin 5-HT2A receptor, 28.5 nM and 71.3 nM (13%) at the serotonin 5-HT2B receptor, and 18.8 nM and 18.8 nM (83%) at the serotonin 5-HT2C receptor. Hence, it is a near-full agonist of the serotonin 5-HT2C receptor, a moderate-efficacy partial agonist of the serotonin 5-HT2A receptor, and a very weak partial agonist or antagonist of the serotonin 5-HT2B receptor. Besides for the serotonin 5-HT2 receptors, PNU-22394 shows very weak affinity for the imidazoline I2 receptor (Ki = 1,030 nM).
PNU-22394 produces anorectic effects and weight loss in both animals and humans as well as pro-cognitive-like effects in animals. The anorectic effects of PNU-22394 in animals can be blocked by the selective serotonin 5-HT2C receptor antagonist SB-242084. PNU-22394 produced side effects in humans including headache, anxiety, nausea, and vomiting, but with rapid tolerance to these side effects that developed within 4 days. Despite its activity as a potent serotonin 5-HT2A receptor agonist, PNU-22394 did not produce hallucinogenic effects in humans.
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