Chemistry:ORG-12962

From HandWiki

ORG-12962 is a serotonin 5-HT2 receptor agonist of the pyridinylpiperazine family which was under development for the treatment of major depressive disorder but was never marketed.[1][2]

It acts preferentially as a partial agonist of the serotonin 5-HT2C receptor (Ki = 12 nM; EC50 = 97.7 nM; Emax = 62%).[3][4][5] However, to a lesser extent, it is also a partial agonist of the serotonin 5-HT2A receptor (Ki = 65 nM; EC50 = 417 nM; Emax = 54%) and of the serotonin 5-HT2B receptor (EC50 = 525 nM; Emax = 41%).[3][4] In addition, ORG-12962 shows affinity for other serotonin receptors, such as the serotonin 5-HT1B receptor (Ki = 100 nM) and to a much lesser extent the serotonin 5-HT1A receptor (Ki = 2,500 nM).[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 selectivity in vivo over the hallucinogenic serotonin 5-HT2A receptor.[4][6]

ORG-12962 was first described in the scientific literature by 1995.[7][8] It was developed by Organon.[1][2] The drug reached phase 2 clinical trials for depression prior to the discontinuation of its development.[1][2]

See also

References

  1. ↑ 1.0 1.1 1.2 "ORG 12962". 22 January 2007. https://adisinsight.springer.com/drugs/800009203. 
  2. ↑ 2.0 2.1 2.2 "Delving into the Latest Updates on Org-12962 with Synapse". 17 January 2026. https://synapse.patsnap.com/drug/737b18cb96b44d95b668354b2d5c67e9. 
  3. ↑ 3.0 3.1 "Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells". British Journal of Pharmacology 128 (1): 13–20. September 1999. doi:10.1038/sj.bjp.0702751. PMID 10498829. 
  4. ↑ 4.0 4.1 4.2 "5-HT2C ligands: recent progress". Progress in Medicinal Chemistry 46: 281–390. 2008. doi:10.1016/S0079-6468(07)00006-9. ISBN 9780444530189. PMID 18381128. "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].". 
  5. ↑ 5.0 5.1 "5-Hydroxytryptamine 2C (5-HT2C) receptor agonists as potential antiobesity agents". J Med Chem 49 (14): 4023–4034. July 2006. doi:10.1021/jm058240i. PMID 16821762. "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". 
  6. ↑ 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
  7. ↑ Price, Gary W (1995). "Meeting Highlights: 3rd IUPHAR Satellite Meeting on Serotonin July 30 - August 3 1994, Chicago, USA: Serotonin 94". Expert Opinion on Investigational Drugs 4 (1): 45–47. doi:10.1517/13543784.4.1.45. ISSN 1354-3784. http://www.tandfonline.com/doi/full/10.1517/13543784.4.1.45. Retrieved 19 January 2026. 
  8. ↑ Kerrigan, Frank (1998). "Antidepressant patents: 1995 - 1997". Expert Opinion on Therapeutic Patents 8 (4): 439–460. doi:10.1517/13543776.8.4.439. ISSN 1354-3776. http://www.tandfonline.com/doi/full/10.1517/13543776.8.4.439. Retrieved 19 January 2026. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:ORG-12962&oldid=4243843"