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CGS-12066

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CGS-12066
Clinical data
Other namesCGS12066; CGS-12066A; CGS12066A; CGS-12066B; CGS12066B
Routes of
administration		Unknown[1]
Drug classSerotonin 5-HT1B receptor agonist
ATC code
  • None
Identifiers
  • 4-(4-methylpiperazin-1-yl)-7-(trifluoromethyl)pyrrolo[1,2-a]quinoxaline
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H17F3N4
Molar mass334.346 g·mol−1
3D model (JSmol)
  • CN1CCN(CC1)C2=NC3=C(C=CC(=C3)C(F)(F)F)N4C2=CC=C4
  • InChI=1S/C17H17F3N4/c1-22-7-9-23(10-8-22)16-15-3-2-6-24(15)14-5-4-12(17(18,19)20)11-13(14)21-16/h2-6,11H,7-10H2,1H3
  • Key:LXFHSCDLMBZYKY-UHFFFAOYSA-N

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

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References

[edit]
  1. 1 2 3 4 "CGS 12066B". AdisInsight. 24 January 1996. Retrieved 19 January 2026.
  2. 1 2 "Delving into the Latest Updates on CGS-12066B with Synapse". Synapse. 15 May 2025. Retrieved 19 January 2026.
  3. 1 2 Middlemiss DN, Hutson PH (1990). "The 5-HT1B receptors". Annals of the New York Academy of Sciences. 600: 132–47, discussion 347–48. doi:10.1111/j.1749-6632.1990.tb16878.x. PMID 2252306.
  4. 1 2 3 4 Neale RF, Fallon SL, Boyar WC, Wasley JW, Martin LL, Stone GA, et al. (April 1987). "Biochemical and pharmacological characterization of CGS 12066B, a selective serotonin-1B agonist". European Journal of Pharmacology. 136 (1): 1–9. doi:10.1016/0014-2999(87)90772-2. PMID 3496228.
  5. ↑ Berendsen HH, Broekkamp CL (November 1990). "Behavioural evidence for functional interactions between 5-HT-receptor subtypes in rats and mice". British Journal of Pharmacology. 101 (3): 667–673. doi:10.1111/j.1476-5381.1990.tb14138.x. PMC 1917735. PMID 2150180.
  6. ↑ Schoeffter P, Hoyer D (June 1989). "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. doi:10.1007/BF00168661. PMID 2770889.
  7. ↑ Knight AR, Misra A, Quirk K, Benwell K, Revell D, Kennett G, et al. (August 2004). "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. doi:10.1007/s00210-004-0951-4. PMID 15322733. S2CID 8938111.
  8. ↑ Riva MA, Creese I (July 1989). "Comparison of two putatively selective radioligands for labeling central nervous system beta-adrenergic receptors: inadequacy of [3H]dihydroalprenolol". Molecular Pharmacology. 36 (1): 201–210. doi:10.1016/S0026-895X(25)09098-4. PMID 2546050.
  9. ↑ Benjamin D, Lal H, Meyerson LR (1990). "The effects of 5-HT1B characterizing agents in the mouse elevated plus-maze". Life Sciences. 47 (3): 195–203. doi:10.1016/0024-3205(90)90320-q. PMID 1975081.
  10. ↑ Rodgers RJ, Cole JC, Cobain MR, Daly P, Doran PJ, Eells JR, et al. (December 1992). "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. doi:10.1097/00008877-199212000-00009. PMID 11224163.
  11. 1 2 Frances H, Monier C (June 1991). "Tolerance to the behavioural effect of serotonergic (5-HT1B) agonists in the isolation-induced social behavioural deficit test". Neuropharmacology. 30 (6): 623–627. doi:10.1016/0028-3908(91)90082-m. PMID 1833660.
  12. ↑ de Boer SF, Koolhaas JM (December 2005). "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. doi:10.1016/j.ejphar.2005.09.065. PMID 16310183.
  13. ↑ Bell R, Donaldson C, Gracey D (September 1995). "Differential effects of CGS 12066B and CP-94,253 on murine social and agonistic behaviour". Pharmacology, Biochemistry, and Behavior. 52 (1): 7–16. doi:10.1016/0091-3057(95)00077-a. PMID 7501681.
  14. ↑ Cheetham SC, Heal DJ (December 1993). "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. doi:10.1111/j.1476-5381.1993.tb14010.x. PMC 2175846. PMID 8306109.
  15. ↑ Monti JM (August 2011). "Serotonin control of sleep-wake behavior". Sleep Medicine Reviews. 15 (4): 269–281. doi:10.1016/j.smrv.2010.11.003. PMID 21459634.
  16. ↑ Monti JM, Jantos H (2008). "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. Vol. 172. pp. 625–646. doi:10.1016/S0079-6123(08)00929-1. ISBN 978-0-444-53235-0. PMID 18772053.
  17. ↑ Bjorvatn B, Ursin R (June 1994). "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. doi:10.1111/j.1365-2869.1994.tb00112.x. PMID 10607113.
  18. ↑ Bjorvatn B, Neckelmann D, Bjørkum AA, Ursin R (October 1996). "Hypothermia and the 5-HT syndrome induced by CGS 12066B independently of 5-HT(1B) receptor activation". Behavioural Pharmacology. 7 (5): 462–469. PMID 11224442.
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