GR-55562

GR-55562
Clinical data
Other names	GR55562; GR-55,562; GR55,562
Drug class	Serotonin 5-HT1B and 5-HT1D receptor antagonist; Selective serotonin 5-HT1B antagonist
Identifiers
	IUPAC name 3-[3-(dimethylamino)propyl]-4-hydroxy-N-(4-pyridin-4-ylphenyl)benzamide;
CAS Number	159533-26-3;
PubChem CID	128018;
IUPHAR/BPS	113;
ChemSpider	113523;
UNII	QPY74DMU5M;
ChEBI	CHEBI:92813;
ChEMBL	ChEMBL119264;
Chemical and physical data
Formula	C23H25N3O2
Molar mass	375.472 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN(C)CCCC1=C(C=CC(=C1)C(=O)NC2=CC=C(C=C2)C3=CC=NC=C3)O;
	InChI InChI=1S/C23H25N3O2/c1-26(2)15-3-4-19-16-20(7-10-22(19)27)23(28)25-21-8-5-17(6-9-21)18-11-13-24-14-12-18/h5-14,16,27H,3-4,15H2,1-2H3,(H,25,28); Key:ZAGAUUVCYGSPBP-UHFFFAOYSA-N;

GR-55562 is a selective serotonin 5-HT_1B and 5-HT_1D receptor antagonist.^[1] It is one of several selective serotonin 5-HT_1B receptor antagonists used in scientific research.^[2]^[3]

The drug is a silent antagonist of the serotonin 5-HT_1B receptor, unlike the related agent GR-127935.^[1]^[4] GR-55562 has around 10-fold selectivity for the serotonin 5-HT_1B receptor over the serotonin 5-HT_1D receptor and has only weak affinity for a number of other serotonin receptors.^[4]

It is ineffective in attenuating MDMA-induced prosocial behavior in animals.^[5]^[6] Conversely, the serotonin 5-HT_1A receptor antagonist WAY-100635 can abolish MDMA-induced prosocial behavior.^[5]^[6]

^ ^a ^b Halazy S, Lamothe M, Jorand-Lebrun C (1997). "5-HT_1B/1Dantagonists and depression". Expert Opinion on Therapeutic Patents. 7 (4). Informa Healthcare: 339–352. doi:10.1517/13543776.7.4.339. ISSN 1354-3776. However, as mentioned above, it was later found that GR-127935 is not a silent antagonist at human 5- HT1B/1D sites. More recent investigations from Glaxo and others have shown that, unlike GR-127935, GR55562 could be characterised as a silent, potent and selective h5-HT1B receptor antagonist [43]. However, so far no results have been disclosed concerning the ability of this particular compound to antagonise central presynaptic 5-HT1B receptors upon systemic administration.
^ Alexander SP, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, et al. (December 2019). "THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors". British Journal of Pharmacology. 176 (Suppl 1): S21–S141. doi:10.1111/bph.14748. PMC 6844580. PMID 31710717.
^ Hannon J, Hoyer D (December 2008). "Molecular biology of 5-HT receptors". Behavioural Brain Research. 195 (1): 198–213. doi:10.1016/j.bbr.2008.03.020. PMID 18571247.
^ ^a ^b "GR 55562 dihydrochloride Supplier". Tocris Bioscience. Retrieved 27 October 2024. GR 55562 dihydrochloride is a selective competitive 5-HT1B (5-HT1Dβ) silent antagonist with pKB values of 7.3 and 6.3 for human cloned 5-HT1B and 5-HT1D receptors respectively and only weak binding at a number of other 5-HT subtypes.
^ ^a ^b Blanco-Gandía MC, Mateos-García A, García-Pardo MP, Montagud-Romero S, Rodríguez-Arias M, Miñarro J, et al. (September 2015). "Effect of drugs of abuse on social behaviour: a review of animal models". Behavioural Pharmacology. 26 (6): 541–570. doi:10.1097/FBP.0000000000000162. PMID 26221831.
^ ^a ^b Morley KC, Arnold JC, McGregor IS (June 2005). "Serotonin (1A) receptor involvement in acute 3,4-methylenedioxymethamphetamine (MDMA) facilitation of social interaction in the rat". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 29 (5): 648–657. doi:10.1016/j.pnpbp.2005.04.009. PMID 15908091.

[HalazyLamotheJorand-Lebrun1997-1] Halazy S, Lamothe M, Jorand-Lebrun C (1997). "5-HT_1B/1Dantagonists and depression". Expert Opinion on Therapeutic Patents. 7 (4). Informa Healthcare: 339–352. doi:10.1517/13543776.7.4.339. ISSN 1354-3776. However, as mentioned above, it was later found that GR-127935 is not a silent antagonist at human 5- HT1B/1D sites. More recent investigations from Glaxo and others have shown that, unlike GR-127935, GR55562 could be characterised as a silent, potent and selective h5-HT1B receptor antagonist [43]. However, so far no results have been disclosed concerning the ability of this particular compound to antagonise central presynaptic 5-HT1B receptors upon systemic administration.

[AlexanderChristopoulosDavenport2019-2] Alexander SP, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, et al. (December 2019). "THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors". British Journal of Pharmacology. 176 (Suppl 1): S21–S141. doi:10.1111/bph.14748. PMC 6844580. PMID 31710717.

[HannonHoyer2008-3] Hannon J, Hoyer D (December 2008). "Molecular biology of 5-HT receptors". Behavioural Brain Research. 195 (1): 198–213. doi:10.1016/j.bbr.2008.03.020. PMID 18571247.

[Tocris-4] "GR 55562 dihydrochloride Supplier". Tocris Bioscience. Retrieved 27 October 2024. GR 55562 dihydrochloride is a selective competitive 5-HT1B (5-HT1Dβ) silent antagonist with pKB values of 7.3 and 6.3 for human cloned 5-HT1B and 5-HT1D receptors respectively and only weak binding at a number of other 5-HT subtypes.

[Blanco-GandíaMateos-GarcíaGarcía-Pardo2015-5] Blanco-Gandía MC, Mateos-García A, García-Pardo MP, Montagud-Romero S, Rodríguez-Arias M, Miñarro J, et al. (September 2015). "Effect of drugs of abuse on social behaviour: a review of animal models". Behavioural Pharmacology. 26 (6): 541–570. doi:10.1097/FBP.0000000000000162. PMID 26221831.

[MorleyArnoldMcGregor2005-6] Morley KC, Arnold JC, McGregor IS (June 2005). "Serotonin (1A) receptor involvement in acute 3,4-methylenedioxymethamphetamine (MDMA) facilitation of social interaction in the rat". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 29 (5): 648–657. doi:10.1016/j.pnpbp.2005.04.009. PMID 15908091.

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