SDZ SER-082

SDZ SER-082
Clinical data
Other names	SDZ SER-082; SDZ SER082
Drug class	Selective serotonin 5-HT2B and 5-HT2C receptor antagonist or weak partial agonist
Identifiers
	IUPAC name (2R,7S)-4-methyl-4,9-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(15),12(16),13-triene;
CAS Number	141474-54-6 ;
PubChem CID	9859407;
IUPHAR/BPS	195;
ChemSpider	8035107 ;
UNII	M7FHF24Q22;
ChEMBL	ChEMBL316069;
CompTox Dashboard (EPA)	DTXSID001028477 ;
Chemical and physical data
Formula	C15H20N2
Molar mass	228.339 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1CC[C@@H]2CN3CCC4=C3C(=CC=C4)[C@@H]2C1;
	InChI InChI=1S/C15H20N2/c1-16-7-5-12-9-17-8-6-11-3-2-4-13(15(11)17)14(12)10-16/h2-4,12,14H,5-10H2,1H3/t12-,14-/m1/s1 ; Key:YASBOGFWAMXINH-TZMCWYRMSA-N ;
	(verify)

SER-082, or SDZ SER-082, is a selective serotonin 5-HT_2B and 5-HT_2C receptor antagonist or weak partial agonist with an ergoline-like structure which is used in scientific research.^[1]^[2]^[3] It shows similar affinity for the serotonin 5-HT_2B and 5-HT_2C receptors and has ~40-fold higher affinity for the serotonin 5-HT_2C receptor over the closely related serotonin 5-HT_2A receptor.^[1]^[3]

Usages

It has been used in animal studies into the behavioural effects of the different 5-HT₂ subtypes,^[4]^[5]^[6] and how they influence the effects of other drugs such as cocaine.^[7]^[8]^[9] The drug has been found to have no effect on anxiety in multiple paradigms in rodents.^[10] In contrast to other serotonin 5-HT_2C receptor antagonists, SER-082 does not produce hyperlocomotion in rodents, and instead can produce hypolocomotion at high doses that is independent of the serotonin 5-HT_2C receptor.^[11]

It fails to block the effects of serotonergic psychedelics in multiple behavioral paradigms, in contrast to serotonin 5-HT_2A receptor antagonists.^[12]^[13]^[14] However, the hypolocomotion induced by high doses of the phenethylamine psychedelic DOI can be attenuated by SER-082.^[15] Conversely, the drug was ineffective against the hypolocomotion induced by the tryptamine psychedelic 5-MeO-DMT, whereas the serotonin 5-HT_1A receptor antagonist WAY-100635 was effective.^[16]

References

^ ^a ^b van Wijngaarden I, Soudijn W (1997). "5-HT2A, 5-HT2B and 5-HT2C receptor ligands". Pharmacochemistry Library. Vol. 27. Elsevier. pp. 161–197. doi:10.1016/s0165-7208(97)80013-x. ISBN 978-0-444-82041-9.
^ Oh SJ, Ha HJ, Chi DY, Lee HK (July 2001). "Serotonin receptor and transporter ligands - current status". Current Medicinal Chemistry. 8 (9): 999–1034. doi:10.2174/0929867013372599. PMID 11472239.
^ ^a ^b Nozulak J, Kalkman HO, Floersheim P, Hoyer D, Schoeffter P, Buerki HR (January 1995). "(+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo[1,7- bc][2,6]-naphthyridine: a 5-HT2C/2B receptor antagonist with low 5-HT2A receptor affinity". Journal of Medicinal Chemistry. 38 (1): 28–33. doi:10.1021/jm00001a007. PMID 7837236.
^ Mora PO, Netto CF, Graeff FG (December 1997). "Role of 5-HT2A and 5-HT2C receptor subtypes in the two types of fear generated by the elevated T-maze". Pharmacology, Biochemistry, and Behavior. 58 (4): 1051–1057. doi:10.1016/S0091-3057(97)00057-9. PMID 9408213. S2CID 11115355.
^ Dave KD, Harvey JA, Aloyo VJ (May 2002). "A novel behavioral model that discriminates between 5-HT2A and 5-HT2C receptor activation". Pharmacology, Biochemistry, and Behavior. 72 (1–2): 371–378. doi:10.1016/S0091-3057(01)00767-5. PMID 11900808. S2CID 36921090.
^ Hawkins MF, Uzelac SM, Hearn JK, Baumeister AA (October 2008). "Effects of selective serotonin2 ligands on behaviors evoked by stress in the rat". Pharmacology, Biochemistry, and Behavior. 90 (4): 632–639. doi:10.1016/j.pbb.2008.05.006. PMID 18572227. S2CID 25959070.
^ Filip M, Bubar MJ, Cunningham KA (September 2004). "Contribution of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes to the hyperlocomotor effects of cocaine: acute and chronic pharmacological analyses". The Journal of Pharmacology and Experimental Therapeutics. 310 (3): 1246–1254. doi:10.1124/jpet.104.068841. PMID 15131246. S2CID 25809734.
^ Filip M (2005). "Role of serotonin (5-HT)2 receptors in cocaine self-administration and seeking behavior in rats". Pharmacological Reports. 57 (1): 35–46. PMID 15849375.
^ Filip M, Bubar MJ, Cunningham KA (January 2006). "Contribution of serotonin (5-HT) 5-HT2 receptor subtypes to the discriminative stimulus effects of cocaine in rats". Psychopharmacology. 183 (4): 482–489. doi:10.1007/s00213-005-0197-y. PMID 16261316. S2CID 23148827.
^ Bourin M, Nic Dhonnchadha BA (2005). "5-HT 2 receptors and anxiety". Drug Development Research. 65 (3): 133–140. doi:10.1002/ddr.20016. ISSN 0272-4391.
^ Fletcher PJ, Tampakeras M, Sinyard J, Slassi A, Isaac M, Higgins GA (September 2009). "Characterizing the effects of 5-HT(2C) receptor ligands on motor activity and feeding behaviour in 5-HT(2C) receptor knockout mice". Neuropharmacology. 57 (3): 259–267. doi:10.1016/j.neuropharm.2009.05.011. PMID 19501602.
^ Nichols D, Nichols CD (2021). "The Pharmacology of Psychedelics". In Grob C, Grigsby J (eds.). Handbook of Medical Hallucinogens. Guilford Publications. pp. 3–28. ISBN 978-1-4625-4544-5. Retrieved 17 January 2025. M 100907, but not the 5-HT2C/2B antagonist SER-082, can block most of the behavioral effects of DOI in the BPM paradigm, which are therefore likely mediated by activation of 5-HT2A receptors (Krebs-Thomson, Paulus, & Geyer, 1998). [...] Furthermore, 5-HT2B antagonists (e.g., SB 200,646A, SB 206,553, and SER-082) and the selective 5-HT2C antagonist SB 242,084, consistently fail to block the effects of hallucinogens in a variety of behavioral paradigms (Halberstadt et al., 2016; Ouagazzal et al., 2001; Schreiber et al., 1994; Sipes & Geyer, 1995; Smith et al., 1999; Wettstein, Host, & Hitchcock, 1999; Winter, Rice, Amorosi, & Rabin, 2007).
^ Willins DL, Meltzer HY (August 1997). "Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats". The Journal of Pharmacology and Experimental Therapeutics. 282 (2): 699–706. doi:10.1016/S0022-3565(24)36840-5. PMID 9262333.
^ Krebs-Thomson K, Paulus MP, Geyer MA (May 1998). "Effects of hallucinogens on locomotor and investigatory activity and patterns: influence of 5-HT2A and 5-HT2C receptors". Neuropsychopharmacology. 18 (5): 339–351. doi:10.1016/S0893-133X(97)00164-4. PMID 9536447.
^ Halberstadt AL, van der Heijden I, Ruderman MA, Risbrough VB, Gingrich JA, Geyer MA, et al. (July 2009). "5-HT(2A) and 5-HT(2C) receptors exert opposing effects on locomotor activity in mice". Neuropsychopharmacology. 34 (8): 1958–1967. doi:10.1038/npp.2009.29. PMC 2697271. PMID 19322172.
^ Krebs-Thomson K, Ruiz EM, Masten V, Buell M, Geyer MA (December 2006). "The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats". Psychopharmacology. 189 (3): 319–329. doi:10.1007/s00213-006-0566-1. PMID 17013638.

[vanWijngaardenSoudijn1997-1] van Wijngaarden I, Soudijn W (1997). "5-HT2A, 5-HT2B and 5-HT2C receptor ligands". Pharmacochemistry Library. Vol. 27. Elsevier. pp. 161–197. doi:10.1016/s0165-7208(97)80013-x. ISBN 978-0-444-82041-9.

[OhHaChi2001-2] Oh SJ, Ha HJ, Chi DY, Lee HK (July 2001). "Serotonin receptor and transporter ligands - current status". Current Medicinal Chemistry. 8 (9): 999–1034. doi:10.2174/0929867013372599. PMID 11472239.

[NozulakKalkmanFloersheim1995-3] Nozulak J, Kalkman HO, Floersheim P, Hoyer D, Schoeffter P, Buerki HR (January 1995). "(+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo[1,7- bc][2,6]-naphthyridine: a 5-HT2C/2B receptor antagonist with low 5-HT2A receptor affinity". Journal of Medicinal Chemistry. 38 (1): 28–33. doi:10.1021/jm00001a007. PMID 7837236.

[pmid9408213-4] Mora PO, Netto CF, Graeff FG (December 1997). "Role of 5-HT2A and 5-HT2C receptor subtypes in the two types of fear generated by the elevated T-maze". Pharmacology, Biochemistry, and Behavior. 58 (4): 1051–1057. doi:10.1016/S0091-3057(97)00057-9. PMID 9408213. S2CID 11115355.

[pmid11900808-5] Dave KD, Harvey JA, Aloyo VJ (May 2002). "A novel behavioral model that discriminates between 5-HT2A and 5-HT2C receptor activation". Pharmacology, Biochemistry, and Behavior. 72 (1–2): 371–378. doi:10.1016/S0091-3057(01)00767-5. PMID 11900808. S2CID 36921090.

[pmid18572227-6] Hawkins MF, Uzelac SM, Hearn JK, Baumeister AA (October 2008). "Effects of selective serotonin2 ligands on behaviors evoked by stress in the rat". Pharmacology, Biochemistry, and Behavior. 90 (4): 632–639. doi:10.1016/j.pbb.2008.05.006. PMID 18572227. S2CID 25959070.

[pmid15131246-7] Filip M, Bubar MJ, Cunningham KA (September 2004). "Contribution of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes to the hyperlocomotor effects of cocaine: acute and chronic pharmacological analyses". The Journal of Pharmacology and Experimental Therapeutics. 310 (3): 1246–1254. doi:10.1124/jpet.104.068841. PMID 15131246. S2CID 25809734.

[pmid15849375-8] Filip M (2005). "Role of serotonin (5-HT)2 receptors in cocaine self-administration and seeking behavior in rats". Pharmacological Reports. 57 (1): 35–46. PMID 15849375.

[pmid16261316-9] Filip M, Bubar MJ, Cunningham KA (January 2006). "Contribution of serotonin (5-HT) 5-HT2 receptor subtypes to the discriminative stimulus effects of cocaine in rats". Psychopharmacology. 183 (4): 482–489. doi:10.1007/s00213-005-0197-y. PMID 16261316. S2CID 23148827.

[BourinNicDhonnchadha2005-10] Bourin M, Nic Dhonnchadha BA (2005). "5-HT 2 receptors and anxiety". Drug Development Research. 65 (3): 133–140. doi:10.1002/ddr.20016. ISSN 0272-4391.

[FletcherTampakerasSinyard2009-11] Fletcher PJ, Tampakeras M, Sinyard J, Slassi A, Isaac M, Higgins GA (September 2009). "Characterizing the effects of 5-HT(2C) receptor ligands on motor activity and feeding behaviour in 5-HT(2C) receptor knockout mice". Neuropharmacology. 57 (3): 259–267. doi:10.1016/j.neuropharm.2009.05.011. PMID 19501602.

[NicholsNichols2021-12] Nichols D, Nichols CD (2021). "The Pharmacology of Psychedelics". In Grob C, Grigsby J (eds.). Handbook of Medical Hallucinogens. Guilford Publications. pp. 3–28. ISBN 978-1-4625-4544-5. Retrieved 17 January 2025. M 100907, but not the 5-HT2C/2B antagonist SER-082, can block most of the behavioral effects of DOI in the BPM paradigm, which are therefore likely mediated by activation of 5-HT2A receptors (Krebs-Thomson, Paulus, & Geyer, 1998). [...] Furthermore, 5-HT2B antagonists (e.g., SB 200,646A, SB 206,553, and SER-082) and the selective 5-HT2C antagonist SB 242,084, consistently fail to block the effects of hallucinogens in a variety of behavioral paradigms (Halberstadt et al., 2016; Ouagazzal et al., 2001; Schreiber et al., 1994; Sipes & Geyer, 1995; Smith et al., 1999; Wettstein, Host, & Hitchcock, 1999; Winter, Rice, Amorosi, & Rabin, 2007).

[WillinsMeltzer1997-13] Willins DL, Meltzer HY (August 1997). "Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats". The Journal of Pharmacology and Experimental Therapeutics. 282 (2): 699–706. doi:10.1016/S0022-3565(24)36840-5. PMID 9262333.

[Krebs-ThomsonPaulusGeyer1998-14] Krebs-Thomson K, Paulus MP, Geyer MA (May 1998). "Effects of hallucinogens on locomotor and investigatory activity and patterns: influence of 5-HT2A and 5-HT2C receptors". Neuropsychopharmacology. 18 (5): 339–351. doi:10.1016/S0893-133X(97)00164-4. PMID 9536447.

[HalberstadtvanderHeijdenRuderman2009-15] Halberstadt AL, van der Heijden I, Ruderman MA, Risbrough VB, Gingrich JA, Geyer MA, et al. (July 2009). "5-HT(2A) and 5-HT(2C) receptors exert opposing effects on locomotor activity in mice". Neuropsychopharmacology. 34 (8): 1958–1967. doi:10.1038/npp.2009.29. PMC 2697271. PMID 19322172.

[Krebs-ThomsonRuizMasten2006-16] Krebs-Thomson K, Ruiz EM, Masten V, Buell M, Geyer MA (December 2006). "The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats". Psychopharmacology. 189 (3): 319–329. doi:10.1007/s00213-006-0566-1. PMID 17013638.

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SDZ SER-082

Usages

See also

References

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