Chemistry:SB-242084

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SB-242084 is a selective serotonin 5-HT2C receptor antagonist which is used in scientific research.[1]

It has anxiolytic effects-like effects in rodents,[2] and enhances dopamine signalling in the limbic system,[3] as well as having complex effects on the dopamine release produced by cocaine, increasing it in some brain regions[4][5] but reducing it in others.[6][7] In animal studies, SB-242084 produced stimulant-type activity and reinforcing effects, somewhat similar to but much weaker than cocaine or amphetamines.[8][9] It is self-administered by monkeys.[9] The drug has been found to increase dopamine levels in the striatum in rats and in the nucleus accumbens in monkeys by about 200%.[10] It potentiates the hyperlocomotion induced by amphetamine, methylphenidate, cocaine, MDMA, fenfluramine, nicotine, and morphine in rodents.[11] Local injection of SB-242084 into the nucleus accumbens augments MDMA-induced conditioned place preference (CPP) and dopamine release in this area in rodents.[12]

The drug has been shown to increase the effectiveness of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants in animals, and may also reduce their side effects.[13][14] SSRIs acutely reduce social interaction in rodents, thought to be an anxiogenic response, and this effect can be reversed by SB-242084.[15][16] SB-242084 has been found to reverse the anxiogenic effects of meta-chlorophenylpiperazine (mCPP) in rodents as well.[15] In addition, SSRIs have been found to acutely induce hypolocomotion, which can be reversed by SB-242084.[15][17][18]

SB-242084 was under development by GlaxoSmithKline for the treatment of anxiety disorders in the late 1990s.[19] However, its development looks to have been abandoned.[19]

See also

References

  1. ↑ "SB 242084, a selective and brain penetrant 5-HT2C receptor antagonist". Neuropharmacology 36 (4–5): 609–20. 1997. doi:10.1016/S0028-3908(97)00038-5. PMID 9225286. 
  2. ↑ "Influence of the 5-HT2C receptor antagonist, SB-242084, in tests of anxiety". Pharmacology, Biochemistry, and Behavior 71 (4): 615–625. April 2002. doi:10.1016/S0091-3057(01)00713-4. PMID 11888553. 
  3. ↑ "SB 242084, a selective serotonin2C receptor antagonist, increases dopaminergic transmission in the mesolimbic system". Neuropharmacology 38 (8): 1195–205. August 1999. doi:10.1016/S0028-3908(99)00047-7. PMID 10462132. 
  4. ↑ "In vivo evidence that 5-HT2C receptor antagonist but not agonist modulates cocaine-induced dopamine outflow in the rat nucleus accumbens and striatum". Neuropsychopharmacology 29 (2): 319–26. February 2004. doi:10.1038/sj.npp.1300329. PMID 14560323. 
  5. ↑ "Region-dependent regulation of mesoaccumbens dopamine neurons in vivo by the constitutive activity of central serotonin2C receptors". Journal of Neurochemistry 99 (4): 1311–9. November 2006. doi:10.1111/j.1471-4159.2006.04188.x. PMID 17018023. 
  6. ↑ "Differential regulation of the mesoaccumbens dopamine circuit by serotonin2C receptors in the ventral tegmental area and the nucleus accumbens: an in vivo microdialysis study with cocaine". Neuropsychopharmacology 33 (2): 237–46. January 2008. doi:10.1038/sj.npp.1301414. PMID 17429406. 
  7. ↑ "Serotonin2C receptors in the medial prefrontal cortex facilitate cocaine-induced dopamine release in the rat nucleus accumbens". Neuropharmacology 56 (2): 507–13. February 2009. doi:10.1016/j.neuropharm.2008.10.005. PMID 18977370. 
  8. ↑ "The serotonin 2C receptor antagonist SB 242084 exhibits abuse-related effects typical of stimulants in squirrel monkeys". The Journal of Pharmacology and Experimental Therapeutics 342 (3): 761–769. September 2012. doi:10.1124/jpet.112.195156. PMID 22685342. 
  9. ↑ 9.0 9.1 "Targeting the 5-HT2C Receptor in Biological Context and the Current State of 5-HT2C Receptor Ligand Development". Curr Top Med Chem 19 (16): 1381–1398. 2019. doi:10.2174/1568026619666190709101449. PMID 31288724. "[...] pretreatment with a selective 5-HT2CR antagonist enhanced self-administration of low doses of cocaine and cocaine-evoked reinstatement of drug-seeking, while the selective 5-HT2CR antagonist SB242084 is self-administered in primates [73–76].". 
  10. ↑ "Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys". Exp Clin Psychopharmacol 22 (3): 274–284. June 2014. doi:10.1037/a0036595. PMID 24796848. "A corollary of this proposition is that antagonists at 5-HT2C receptors may block endogenous serotonergic tone at these receptors and thereby disinhibit mesolimbic DA neurons. In support of this idea, 5-HT2C antagonists including SB 242,084 have been shown to increase firing rates of DA neurons and produce modest but significant (~200%) increases in DA levels in rat striatum and squirrel monkey nucleus accumbens (but not squirrel monkey caudate) (Alex et al. 2005; Di Giovanni et al. 1999; Manvich et al. 2012b).". 
  11. ↑ "The effects of the 5-HT(2C) receptor antagonist SB242084 on locomotor activity induced by selective, or mixed, indirect serotonergic and dopaminergic agonists". Psychopharmacology (Berl) 187 (4): 515–525. September 2006. doi:10.1007/s00213-006-0453-9. PMID 16832658. 
  12. ↑ "5-HT2C receptors in the nucleus accumbens constrain the rewarding effects of MDMA". Mol Psychiatry 30 (11): 5405–5416. November 2025. doi:10.1038/s41380-025-03128-4. PMID 40707786. 
  13. ↑ "Inactivation of 5-HT(2C) receptors potentiates consequences of serotonin reuptake blockade". Neuropsychopharmacology 29 (10): 1782–1789. October 2004. doi:10.1038/sj.npp.1300474. PMID 15138437. 
  14. ↑ "Acute selective serotonin reuptake inhibitors increase conditioned fear expression: blockade with a 5-HT(2C) receptor antagonist". Biological Psychiatry 62 (10): 1111–1118. November 2007. doi:10.1016/j.biopsych.2006.11.023. PMID 17524369. 
  15. ↑ 15.0 15.1 15.2 "Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635". Int J Neuropsychopharmacol 4 (4): 399–408. December 2001. doi:10.1017/S1461145701002632. PMID 11806866. 
  16. ↑ "Citalopram reduces social interaction in rats by activation of serotonin (5-HT)(2C) receptors". Neuropharmacology 39 (6): 1114–1117. April 2000. doi:10.1016/s0028-3908(99)00268-3. PMID 10727723. 
  17. ↑ "Chronic treatment with fluvoxamine desensitizes 5-HT2C receptor-mediated hypolocomotion in rats". Pharmacol Biochem Behav 78 (4): 683–689. August 2004. doi:10.1016/j.pbb.2004.05.003. PMID 15301922. 
  18. ↑ "[Effects of fluoxetine on locomotor activity: possible involvement of dopamine]" (in Russian). Zh Vyssh Nerv Deiat Im I P Pavlova 56 (4): 523–528. 2006. PMID 17025197. 
  19. ↑ 19.0 19.1 "SB 242084". 26 July 2002. https://adisinsight.springer.com/drugs/800009495. 



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