It acts preferentially as a partial agonist of the serotonin 5-HT2C receptor (Ki = 12nM; EC50Tooltip half-maximal effective concentration = 97.7nM; EmaxTooltip maximal efficacy = 62%).[3][4][5] However, to a lesser extent, it is also a partial agonist of the serotonin 5-HT2A receptor (Ki = 65nM; EC50 = 417nM; EmaxTooltip maximal efficacy = 54%) and of the serotonin 5-HT2B receptor (EC50 = 525nM; Emax = 41%).[3][4] In addition, ORG-12962 shows affinity for other serotonin receptors, such as the serotonin 5-HT1B receptor (Ki = 100nM) and to a much lesser extent the serotonin 5-HT1A receptor (Ki = 2,500nM).[5]
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 selectivityin vivo over the hallucinogenic serotonin 5-HT2A receptor.[4][6]
^ abcMonck NJ, Kennett GA (2008). "5-HT2C ligands: recent progress". Progress in Medicinal Chemistry. 46: 281–390. doi:10.1016/S0079-6468(07)00006-9. ISBN 9780444530189. PMID18381128. A more selective 5-HT2 agonist, ORG12962 (7) [5] has been assessed in a public-speaking paradigm and was reported to reduce symptoms of anxiety [78]. However, this may have been secondary to the non-specific dizziness and 'spacy' effects induced by the compound [78] possibly due to lack of selectivity over 5-HT2A receptors [5]. [...] Only one other 5-HT2C receptor agonist, ORG12962 (7), has been entered into development for the treatment of anxiety and depression. The development of this compound was halted, presumably due to poor selectivity over 5-HT2A and 5-HT2B receptors [5] which may have caused the side effects described in the panic disorder section (see p. 291) [78].
^ abNilsson BM (July 2006). "5-Hydroxytryptamine 2C (5-HT2C) receptor agonists as potential antiobesity agents". J Med Chem. 49 (14): 4023–4034. doi:10.1021/jm058240i. PMID16821762. Organon (a business unit of Akzo Nobel) has developed the arylpiperazine 18 (ORG-12962), a compound that originally was patented as a preferential 5-HT1B receptor agonist having pKi values of 7.0 and 5.6 for 5-HT1B and 5-HT1A receptors, respectively, in receptor binding studies.89 However, it is now known that 18 also behaves as a partial agonist at human 5-HT2C receptors with low binding selectivity relative to human 5-HT2A receptors (Ki ) 12 and 65 nM, respectively).90 In functional in vitro assays measuring calcium release, this compound displays pEC50 values of 7.01, 6.38, and 6.28, along with relative efficacies of 62%, 54%, and 41%, at the human 5-HT2C, 5-HT2A, and 5-HT2B receptors, respectively.28 Although no study details were provided, 18 has been reported to be effective in an acute rat feeding model (minimum effective dose 3 mg/kg, po).9 This compound has also been evaluated in phase II clinical trials for the potential treatment of depression.91
^Connell, J., Sennef, C., & Deakin, J. F. W. (1999). The effects of ORG 12962, 5-HT2C receptor agonist, in two models of experimentally induced anxiety in healthy female volunteers. International Journal of Neuropsychopharmacology, 2, S136–S137. https://scholar.google.com/scholar?cluster=2357514178179946021
(what is this?) (verify)