Chemistry:CGS-12066

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CGS-12066, also known as CGS-12066A and CGS-12066B, is a predominant serotonin 5-HT1B receptor agonist which was under development for the treatment of anxiety disorders but was never marketed.[1][2][3][4] Its route of administration is unknown.[1]

In terms of affinity, it is moderately (17-fold) selective for the serotonin 5-HT1B receptor over the serotonin 5-HT1A receptor, where it is also an agonist.[3][4][5] Although reported to be a selective serotonin 5-HT1B receptor agonist, it was subsequently found to be equipotent as an agonist of the serotonin 5-HT1B and 5-HT1D receptors.[6] The drug showed weak affinity for the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors (Ki = 871–4,270 nM).[7] It had minimal affinity for various adrenergic and dopamine receptors.[4][8]

CGS-12066 produces anxiolytic-like,[9][10] prosocial,[11] and antiaggressive effects in rodents.[12][13] There is rapid tolerance to its prosocial effects, thought to be due to desensitization of serotonin 5-HT1B receptors.[11] 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-HT1B receptor.[14] It produces wakefulness and reduces slow wave sleep (SWS) and rapid eye movement (REM) sleep in rodents.[15][16][17] Some of the effects of CGS-12066 in animals, such as hypothermia and serotonin behavioral syndrome, are not mediated by the serotonin 5-HT1B receptor.[18]

CGS-12066 was first described in the scientific literature by 1987.[4] It reached the preclinical research stage of development for anxiety disorders prior to the discontinuation of its development in 1995.[1][2]

See also

References

  1. ↑ 1.0 1.1 1.2 "CGS 12066B". 24 January 1996. https://adisinsight.springer.com/drugs/800006033. 
  2. ↑ 2.0 2.1 "Delving into the Latest Updates on CGS-12066B with Synapse". 15 May 2025. https://synapse.patsnap.com/drug/277c773242974f7abcc818c61d49aaa1. 
  3. ↑ 3.0 3.1 "The 5-HT1B receptors". Annals of the New York Academy of Sciences 600: 132–47; discussion 347–48. 1990. doi:10.1111/j.1749-6632.1990.tb16878.x. PMID 2252306. 
  4. ↑ 4.0 4.1 4.2 4.3 "Biochemical and pharmacological characterization of CGS 12066B, a selective serotonin-1B agonist". European Journal of Pharmacology 136 (1): 1–9. April 1987. doi:10.1016/0014-2999(87)90772-2. PMID 3496228. 
  5. ↑ "Behavioural evidence for functional interactions between 5-HT-receptor subtypes in rats and mice". British Journal of Pharmacology 101 (3): 667–673. November 1990. doi:10.1111/j.1476-5381.1990.tb14138.x. PMID 2150180. 
  6. ↑ "Interaction of arylpiperazines with 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors: do discriminatory 5-HT1B receptor ligands exist?". Naunyn-Schmiedeberg's Archives of Pharmacology 339 (6): 675–683. June 1989. doi:10.1007/BF00168661. PMID 2770889. 
  7. ↑ "Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors". Naunyn-Schmiedeberg's Archives of Pharmacology 370 (2): 114–123. August 2004. doi:10.1007/s00210-004-0951-4. PMID 15322733. 
  8. ↑ "Comparison of two putatively selective radioligands for labeling central nervous system beta-adrenergic receptors: inadequacy of [3H]dihydroalprenolol". Molecular Pharmacology 36 (1): 201–210. July 1989. doi:10.1016/S0026-895X(25)09098-4. PMID 2546050. 
  9. ↑ "The effects of 5-HT1B characterizing agents in the mouse elevated plus-maze". Life Sciences 47 (3): 195–203. 1990. doi:10.1016/0024-3205(90)90320-q. PMID 1975081. 
  10. ↑ "Anxiogenic-like effects of fluprazine and eltoprazine in the mouse elevated plus-maze: profile comparisons with 8-OH-DPAT, CGS 12066B, TFMPP and mCPP". Behavioural Pharmacology 3 (6): 621–634. December 1992. doi:10.1097/00008877-199212000-00009. PMID 11224163. 
  11. ↑ 11.0 11.1 "Tolerance to the behavioural effect of serotonergic (5-HT1B) agonists in the isolation-induced social behavioural deficit test". Neuropharmacology 30 (6): 623–627. June 1991. doi:10.1016/0028-3908(91)90082-m. PMID 1833660. 
  12. ↑ "5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis". European Journal of Pharmacology 526 (1–3): 125–139. December 2005. doi:10.1016/j.ejphar.2005.09.065. PMID 16310183. 
  13. ↑ "Differential effects of CGS 12066B and CP-94,253 on murine social and agonistic behaviour". Pharmacology, Biochemistry, and Behavior 52 (1): 7–16. September 1995. doi:10.1016/0091-3057(95)00077-a. PMID 7501681. 
  14. ↑ "Evidence that RU 24969-induced locomotor activity in C57/B1/6 mice is specifically mediated by the 5-HT1B receptor". British Journal of Pharmacology 110 (4): 1621–1629. December 1993. doi:10.1111/j.1476-5381.1993.tb14010.x. PMID 8306109. 
  15. ↑ "Serotonin control of sleep-wake behavior". Sleep Medicine Reviews 15 (4): 269–281. August 2011. doi:10.1016/j.smrv.2010.11.003. PMID 21459634. 
  16. ↑ "The roles of dopamine and serotonin, and of their receptors, in regulating sleep and waking". Serotonin–Dopamine Interaction: Experimental Evidence and Therapeutic Relevance. Progress in Brain Research. 172. 2008. pp. 625–646. doi:10.1016/S0079-6123(08)00929-1. ISBN 978-0-444-53235-0. 
  17. ↑ "Effects of the selective 5-HT1B agonist, CGS 12066B, on sleep/waking stages and EEG power spectrum in rats". Journal of Sleep Research 3 (2): 97–105. June 1994. doi:10.1111/j.1365-2869.1994.tb00112.x. PMID 10607113. 
  18. ↑ "Hypothermia and the 5-HT syndrome induced by CGS 12066B independently of 5-HT(1B) receptor activation". Behavioural Pharmacology 7 (5): 462–469. October 1996. PMID 11224442. 

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