SB-206553

Last updated
SB-206553
SB-206553.svg
Identifiers
  • 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C17H16N4O
Molar mass 292.342 g·mol−1
3D model (JSmol)
  • Cn2ccc(c2c3)cc1c3CCN1C(=O)Nc4cccnc4
  • InChI=1S/C17H16N4O/c1-20-7-4-12-10-16-13(9-15(12)20)5-8-21(16)17(22)19-14-3-2-6-18-11-14/h2-4,6-7,9-11H,5,8H2,1H3,(H,19,22)
  • Key:QJQORSLQNXDVGE-UHFFFAOYSA-N

SB-206553 is a drug which acts as a mixed antagonist for the 5-HT2B and 5-HT2C serotonin receptors. [1] [2] [3]

It has anxiolytic properties in animal studies and interacts with a range of other drugs. [4] [5] [6] [7] [8] [9] [10] [11] [12] It has also been shown to act as a positive allosteric modulator of α7 nicotinic acetylcholine receptors. [13] Modified derivatives of SB-206553 have been used to probe the structure of the 5-HT2B receptor. [14]

SB-206553 was under development by GlaxoSmithKline for the treatment of anxiety disorders in the 1990s. [15] However, its development was discontinued in 1996. [15]

Related Research Articles

<span class="mw-page-title-main">5-HT receptor</span> Class of transmembrane proteins

5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.

<span class="mw-page-title-main">Agomelatine</span> Atypical antidepressant classified primarily as a melatonin receptor agonist

Agomelatine, sold under the brand names Valdoxan and Thymanax, among others, is an atypical antidepressant most commonly used to treat major depressive disorder and generalized anxiety disorder. One review found that it is as effective as other antidepressants with similar discontinuation rates overall but fewer discontinuations due to side effects. Another review also found it was similarly effective to many other antidepressants.

5-HT<sub>2A</sub> receptor Subtype of serotonin receptor

The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations.

5-HT<sub>2C</sub> receptor Serotonin receptor protein distributed mainly in the choroid plexus

The 5-HT2C receptor is a subtype of the 5-HT2 receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, it is a G protein-coupled receptor (GPCR) that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located on the X chromosome. As males have one copy of the gene and females have one of the two copies of the gene repressed, polymorphisms at this receptor can affect the two sexes to differing extent.

5-HT<sub>2B</sub> receptor Mammalian protein found in Homo sapiens

5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, the 5-HT2B receptor is Gq/G11-protein coupled, leading to downstream activation of phospholipase C.

<span class="mw-page-title-main">SB-242084</span> Chemical compound

SB-242084 is a selective antagonist of the serotonin 5-HT2C receptor which is used in scientific research.

<span class="mw-page-title-main">RS-102221</span> Chemical compound

RS-102221 is a drug developed by Hoffmann–La Roche, which was one of the first compounds discovered that acts as a potent and selective antagonist at the serotonin 5-HT2C receptor, with around 100× selectivity over the closely related 5-HT2A and 5-HT2B receptors. It has anxiolytic effects in animal studies, increases the effectiveness of SSRI antidepressants, and shows a complex interaction with cocaine, increasing some effects but decreasing others, reflecting a role for the 5-HT2C receptor in regulation of the dopamine signalling system in the brain.

<span class="mw-page-title-main">BW-723C86</span> Chemical compound

BW-723C86 is a tryptamine derivative drug which acts as a 5-HT2B receptor agonist. It has anxiolytic effects in animal studies, and is also used for investigating the function of the 5-HT2B receptor in a range of other tissues.

<span class="mw-page-title-main">Serotonin releasing agent</span> Class of compounds

A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons, including dopamine and norepinephrine neurons.

<span class="mw-page-title-main">SB-215505</span> Chemical compound

SB-215505 is a drug which acts as a potent and selective antagonist at the serotonin 5-HT2B receptor, with good selectivity over the related 5-HT2A and 5-HT2C receptors. It is used in scientific research into the function of the 5-HT2 family of receptors, especially to study the role of 5-HT2B receptors in the heart, and to distinguish 5-HT2B-mediated responses from those produced by 5-HT2A or 5-HT2C.

<span class="mw-page-title-main">25B-NBOMe</span> Chemical compound

25B-NBOMe is a derivative of the phenethylamine psychedelic 2C-B, discovered in 2004 by Ralf Heim at the Free University of Berlin. It acts as a potent full agonist for the 5HT2A receptor. Duration of effects lasts about 3–10 hours, although the parent compound is rapidly cleared from the blood when used in the radiolabeled form in tracer doses. Recently, Custodio et al. (2019) evaluated the potential involvement of dysregulated dopaminergic system, neuroadaptation, and brain wave changes which may contribute to the rewarding and reinforcing properties of 25B-NBOMe in rodents.

<span class="mw-page-title-main">Serotonin antagonist and reuptake inhibitor</span> Class of drug

Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also antagonize α1-adrenergic receptors. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.

5-HT2C receptor agonists are a class of drugs that activate 5-HT2C receptors. They have been investigated for the treatment of a number of conditions including obesity, psychiatric disorders, sexual dysfunction and urinary incontinence.

<span class="mw-page-title-main">25CN-NBOH</span> Chemical compound

25CN-NBOH is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. It is a member of the NBOMe family of psychedelics.

<span class="mw-page-title-main">SB-243213</span> Chemical compound

SB-243213 is a research chemical which acts as a selective inverse agonist for the 5HT2C receptor and has anxiolytic effects. It has better than 100x selectivity for 5-HT2C over all other receptor subtypes tested, and a longer duration of action compared to older 5-HT2C antagonist ligands.

<span class="mw-page-title-main">Locomotor activity</span> Behavioral measure in animals

Locomotor activity is a measure of animal behavior which is employed in scientific research.

<span class="mw-page-title-main">SB-228357</span> Chemical compound

SB-228357 is a drug which acts as a selective antagonist of the serotonin 5-HT2B and 5-HT2C receptors.

<span class="mw-page-title-main">VU0530244</span> Peripherally selective 5-HT2B antagonist

VU0530244 is a potent, selective, and putatively peripherally restricted serotonin 5-HT2B receptor antagonist which was first described in 2023. Another similar drug, VU0631019, was also described alongside VU0530244. They were identified via high-throughput screening (HTS).

<span class="mw-page-title-main">SB-221284</span> Pharmaceutical compound

SB-221284 is a selective serotonin 5-HT2C and 5-HT2B receptor antagonist which is used in scientific research. Its affinities (Ki) are 2.2 to 2.5 nM for the serotonin 5-HT2C receptor, 2.5 to 12.6 nM for the serotonin 5-HT2B receptor, and 398 to 550 nM for the serotonin 5-HT2A receptor. The drug has 160- to 250-fold selectivity for the serotonin 5-HT2C receptor over the serotonin 5-HT2A receptor. It is said to have been the first serotonin 5-HT2C receptor ligand to show 100-fold selectivity over the serotonin 5-HT2A receptor.

References

  1. ↑ Forbes IT, Ham P, Booth DH, Martin RT, Thompson M, Baxter GS, et al. (July 1995). "5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: a novel 5-HT2C/5-HT2B receptor antagonist with improved affinity, selectivity, and oral activity". Journal of Medicinal Chemistry. 38 (14): 2524–30. doi:10.1021/jm00014a004. PMID   7629791.
  2. ↑ Kennett GA, Wood MD, Bright F, Cilia J, Piper DC, Gager T, et al. (February 1996). "In vitro and in vivo profile of SB 206553, a potent 5-HT2C/5-HT2B receptor antagonist with anxiolytic-like properties". British Journal of Pharmacology. 117 (3): 427–434. doi:10.1111/j.1476-5381.1996.tb15208.x. PMC   1909304 . PMID   8821530.
  3. ↑ Forbes IT, Dabbs S, Duckworth DM, Ham P, Jones GE, King FD, et al. (December 1996). "Synthesis, biological activity, and molecular modeling of selective 5-HT(2C/2B) receptor antagonists". Journal of Medicinal Chemistry. 39 (25): 4966–77. doi:10.1021/jm960571v. PMID   8960557.
  4. ↑ Bromidge SM, Dabbs S, Davies DT, Duckworth DM, Forbes IT, Ham P, et al. (May 1998). "Novel and selective 5-HT2C/2B receptor antagonists as potential anxiolytic agents: synthesis, quantitative structure-activity relationships, and molecular modeling of substituted 1-(3-pyridylcarbamoyl)indolines". Journal of Medicinal Chemistry. 41 (10): 1598–612. doi:10.1021/jm970741j. PMID   9572885.
  5. ↑ Di Matteo V, Di Giovanni G, Di Mascio M, Esposito E (1998). "Selective blockade of serotonin2C/2B receptors enhances dopamine release in the rat nucleus accumbens". Neuropharmacology. 37 (2): 265–72. doi:10.1016/S0028-3908(98)00014-8. PMID   9680252. S2CID   2366196.
  6. ↑ McCreary AC, Cunningham KA (June 1999). "Effects of the 5-HT2C/2B antagonist SB 206553 on hyperactivity induced by cocaine". Neuropsychopharmacology. 20 (6): 556–64. doi: 10.1016/S0893-133X(98)00087-6 . PMID   10327425.
  7. ↑ Di Giovanni G, De Deurwaerdére P, Di Mascio M, Di Matteo V, Esposito E, Spampinato U (1999). "Selective blockade of serotonin-2C/2B receptors enhances mesolimbic and mesostriatal dopaminergic function: a combined in vivo electrophysiological and microdialysis study". Neuroscience. 91 (2): 587–97. doi:10.1016/S0306-4522(98)00655-1. PMID   10366016. S2CID   23080031.
  8. ↑ Takahashi RN, Berton O, Mormède P, Chaouloff F (May 2001). "Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze". Brazilian Journal of Medical and Biological Research. 34 (5): 675–82. doi: 10.1590/s0100-879x2001000500017 . PMID   11323756.
  9. ↑ Porras G, Di Matteo V, Fracasso C, Lucas G, De Deurwaerdère P, Caccia S, et al. (March 2002). "5-HT2A and 5-HT2C/2B receptor subtypes modulate dopamine release induced in vivo by amphetamine and morphine in both the rat nucleus accumbens and striatum". Neuropsychopharmacology. 26 (3): 311–24. doi: 10.1016/S0893-133X(01)00333-5 . PMID   11850146.
  10. ↑ Navailles S, De Deurwaerdère P, Porras G, Spampinato U (February 2004). "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. doi: 10.1038/sj.npp.1300329 . PMID   14560323.
  11. ↑ Canal CE, Olaghere da Silva UB, Gresch PJ, Watt EE, Sanders-Bush E, Airey DC (April 2010). "The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen". Psychopharmacology. 209 (2): 163–74. doi:10.1007/s00213-010-1784-0. PMC   2868321 . PMID   20165943.
  12. ↑ Graves SM, Napier TC (June 2012). "SB 206553, a putative 5-HT2C inverse agonist, attenuates methamphetamine-seeking in rats". BMC Neuroscience. 13: 65. doi: 10.1186/1471-2202-13-65 . PMC   3441362 . PMID   22697313.
  13. ↑ Dunlop J, Lock T, Jow B, Sitzia F, Grauer S, Jow F, et al. (March 2009). "Old and new pharmacology: positive allosteric modulation of the alpha7 nicotinic acetylcholine receptor by the 5-hydroxytryptamine(2B/C) receptor antagonist SB-206553 (3,5-dihydro-5-methyl-N-3-pyridinylbenzo[1,2-b:4,5-b']di pyrrole-1(2H)-carboxamide)". The Journal of Pharmacology and Experimental Therapeutics. 328 (3): 766–76. doi:10.1124/jpet.108.146514. PMID   19050173. S2CID   206500076.
  14. ↑ Kim SK, Li Y, Abrol R, Heo J, Goddard III WA (February 2011). "Predicted structures and dynamics for agonists and antagonists bound to serotonin 5-HT2B and 5-HT2C receptors". Journal of Chemical Information and Modeling. 51 (2): 420–33. doi:10.1021/ci100375b. PMC   3070210 . PMID   21299232.
  15. 1 2 "SB 206553". AdisInsight. 13 August 1996. Retrieved 14 January 2025.


This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.