Chemistry:LY-53857

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LY-53857 is a serotonin 5-HT2 receptor antagonist of the ergoline family which has been widely used in scientific research.[1][2][3][4]

It is a potent antagonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors (Ki = 7.2–50 nM, 6.3–6.9 nM, and 7.9–8.3 nM, respectively).[1][5][6][7][8][9] The drug shows strong selectivity for the serotonin 5-HT2 receptors over the serotonin 5-HT1 and α-adrenergic receptors.[10] Although originally thought to be selective for the serotonin 5-HT2 receptors,[1] LY-53857 was subsequently found to also show significant affinity for the serotonin 5-HT7 receptor (Ki = 100 nM), where it is likewise an antagonist.[11][12] In addition, it shows high affinity for the serotonin 5-HT1F receptor (Ki = 6.87 nM).[13]

It produces antidepressant-like and anxiolytic-like effects in rodents.[3][14][15][16][17][18] The drug has no effect on locomotor activity by itself, but blocks the hyperlocomotion induced by phencyclidine (PCP).[19] In addition, whereas meta-chlorophenylpiperazine (mCPP) produces hypolocomotion by itself, the combination of mCPP with LY-53857 results in mCPP producing hyperlocomotion instead.[20][21] LY-53857 blocks the discriminative stimulus of the psychedelic drugs LSD, mescaline, and DOM in rodent drug discrimination studies.[9][22][23][24] The drug inhibits the hyperthermia induced by the psychedelic drug DOI, by mCPP, and by the serotonin releasing agent para-chloroamphetamine (PCA).[25][26][27]

Analogues of LY-53857 have also been described and include LY-86057 (the N1-desisopropyl analogue), LY-108742 (the N1-methyl analogue), and LY-197541 (the N1-isobutyl analogue).[28][4][29]

LY-53857 was first described in the scientific literature by 1979.[30]

See also

References

  1. ↑ 1.0 1.1 1.2 "A review of central 5-HT receptors and their function". Neuropharmacology 38 (8): 1083–1152. August 1999. doi:10.1016/s0028-3908(99)00010-6. PMID 10462127. 
  2. ↑ "LY53857, a selective and potent serotonergic (5-HT2) receptor antagonist, does not lower blood pressure in the spontaneously hypertensive rat". The Journal of Pharmacology and Experimental Therapeutics 227 (2): 327–332. November 1983. PMID 6313898. 
  3. ↑ 3.0 3.1 "Blockade of a 5-hydroxytryptophan-induced animal model of depression with a potent and selective 5-HT2 receptor antagonist (LY53857)". Biological Psychiatry 20 (6): 592–597. June 1985. doi:10.1016/0006-3223(85)90093-9. PMID 3873259. 
  4. ↑ 4.0 4.1 "Species differences in the pharmacology of the 5-hydroxytryptamine2 receptor: structurally specific differentiation by ergolines and tryptamines". The Journal of Pharmacology and Experimental Therapeutics 265 (3): 1272–1279. June 1993. PMID 8510008. 
  5. ↑ "5-HT2A, 5-HT2B and 5-HT2C receptor ligands". Pharmacochemistry Library. 27. Elsevier. 1997. pp. 161–197. doi:10.1016/s0165-7208(97)80013-x. ISBN 978-0-444-82041-9. 
  6. ↑ "Competitive antagonism by recognized 5-HT2 receptor antagonists at 5-HT1C receptors in pig choroid plexus". Naunyn-Schmiedeberg's Archives of Pharmacology 344 (2): 137–142. August 1991. doi:10.1007/BF00167210. PMID 1944609. 
  7. ↑ "Further characterization of 5-hydroxytryptamine receptors (putative 5-HT2B) in rat stomach fundus longitudinal muscle". British Journal of Pharmacology 112 (1): 323–331. May 1994. doi:10.1111/j.1476-5381.1994.tb13072.x. PMID 8032658. 
  8. ↑ "Further evidence that 5-HT-induced relaxation of pig pulmonary artery is mediated by endothelial 5-HT(2B) receptors". British Journal of Pharmacology 130 (3): 692–698. June 2000. doi:10.1038/sj.bjp.0703341. PMID 10821800. 
  9. ↑ 9.0 9.1 "The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: Antagonist correlation analysis". Psychopharmacology (Berl) 121 (3): 347–356. October 1995. doi:10.1007/BF02246074. PMID 8584617. 
  10. ↑ "Pharmacological activity of the isomers of LY53857, potent and selective 5-HT2 receptor antagonists". The Journal of Pharmacology and Experimental Therapeutics 235 (2): 319–323. November 1985. PMID 4057073. 
  11. ↑ "Serotonin 5-HT7 Receptor Antagonists". Current Medicinal Chemistry-Central Nervous System Agents 4 (3): 203–214. 1 September 2004. doi:10.2174/1568015043356931. 
  12. ↑ "LY215840, a high-affinity 5-HT7 receptor ligand, blocks serotonin-induced relaxation in canine coronary artery". The Journal of Pharmacology and Experimental Therapeutics 277 (3): 1560–1566. June 1996. PMID 8667223. 
  13. ↑ "Pharmacological characteristics of the newly cloned rat 5-hydroxytryptamine2F receptor". Mol Pharmacol 43 (3): 419–426. March 1993. PMID 8450835. 
  14. ↑ "5-HT1C receptor antagonists have anxiolytic-like actions in the rat social interaction model". Psychopharmacology (Berl) 107 (2–3): 379–384. 1992. doi:10.1007/BF02245165. PMID 1352056. 
  15. ↑ "Evidence that 5-HT2c receptor antagonists are anxiolytic in the rat Geller-Seifter model of anxiety". Psychopharmacology (Berl) 114 (1): 90–96. February 1994. doi:10.1007/BF02245448. PMID 7846211. 
  16. ↑ "Effects of 5-HT(2) receptor antagonists on the anti-immobility effects of imipramine in the forced swimming test with mice". European Journal of Pharmacology 427 (3): 221–225. September 2001. doi:10.1016/s0014-2999(01)01240-7. PMID 11567652. 
  17. ↑ "The 5-HT2 receptor antagonist reduces immobility of mice treated with the atypical antidepressant mianserin in the forced swimming test". Biological & Pharmaceutical Bulletin 25 (11): 1479–1481. November 2002. doi:10.1248/bpb.25.1479. PMID 12419964. 
  18. ↑ "Differential effects of the 5-HT2 receptor antagonist on the anti-immobility effects of noradrenaline and serotonin reuptake inhibitors in the forced swimming test". Brain Research 958 (1): 161–165. December 2002. doi:10.1016/s0006-8993(02)03684-3. PMID 12468041. 
  19. ↑ "Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin receptor subtype selective antagonists in mice". Psychopharmacology (Berl) 129 (1): 79–84. January 1997. doi:10.1007/s002130050165. PMID 9122367. 
  20. ↑ "Meta-chlorophenylpiperazine induced changes in locomotor activity are mediated by 5-HT1 as well as 5-HT2C receptors in mice". European Journal of Pharmacology 341 (2–3): 135–138. January 1998. doi:10.1016/s0014-2999(97)01474-x. PMID 9543230. 
  21. ↑ "m-CPP hypolocomotion is selectively antagonized by compounds with high affinity for 5-HT(2C) receptors but not 5-HT(2A) or 5-HT(2B) receptors". Behavioural Pharmacology 12 (8): 613–620. December 2001. doi:10.1097/00008877-200112000-00005. PMID 11856898. 
  22. ↑ "Neuropharmacological reassessment of the discriminative stimulus properties of d-lysergic acid diethylamide (LSD)". Psychopharmacology (Berl) 91 (1): 67–73. 1987. doi:10.1007/BF00690929. PMID 3103161. 
  23. ↑ "Involvement of 5-HT receptor subtypes in the discriminative stimulus properties of mescaline". European Journal of Pharmacology 159 (1): 41–46. January 1989. doi:10.1016/0014-2999(89)90041-1. PMID 2707301. 
  24. ↑ "Mechanistic studies on DOM as a discriminative stimulus". Pharmacology, Biochemistry, and Behavior 23 (6): 937–941. December 1985. doi:10.1016/0091-3057(85)90096-6. PMID 2934750. 
  25. ↑ "Evidence that 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia in rats is mediated by stimulation of 5-HT2A receptors". Psychopharmacology (Berl) 117 (2): 193–199. January 1995. doi:10.1007/BF02245187. PMID 7753967. 
  26. ↑ "Evidence that m-chlorophenylpiperazine-induced hyperthermia in rats is mediated by stimulation of 5-HT2C receptors". Psychopharmacology (Berl) 123 (4): 333–339. February 1996. doi:10.1007/BF02246643. PMID 8867872. 
  27. ↑ "Involvement of the 5-HT(2) receptor in hyperthermia induced by p-chloroamphetamine, a serotonin-releasing drug in mice". European Journal of Pharmacology 403 (3): 225–228. September 2000. doi:10.1016/s0014-2999(00)00585-9. PMID 10973623. 
  28. ↑ "N(1)-substituted ergolines and tryptamines show species differences for the agonist-labeled 5-HT2 receptor". Eur J Pharmacol 239 (1-3): 111–118. August 1993. doi:10.1016/0014-2999(93)90983-o. PMID 8223886. 
  29. ↑ "Species variations in transmembrane region V of the 5-hydroxytryptamine type 2A receptor alter the structure-activity relationship of certain ergolines and tryptamines". Mol Pharmacol 45 (2): 277–286. February 1994. doi:10.1016/S0026-895X(25)09924-9. PMID 8114677. 
  30. ↑ "The effects of metergoline and other serotonin receptor antagonists on serum corticosterone in rats". Endocrinology 105 (4): 923–928. October 1979. doi:10.1210/endo-105-4-923. PMID 477605. 



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